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Lecture 24: Regulation of Gene Expression 2018 - Biology

Lecture 24: Regulation of Gene Expression 2018 - Biology


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Lecture 24: Regulation of Gene Expression 2018

Transcription regulation by the Mediator complex

Recent structural advances based on improvements in electron microscopy methodology have enabled the generation of high-resolution structural models of the mediator of RNA polymerase II transcription (Mediator) complex and of the preinitiation complex (PIC) in the presence of Mediator.

The module composition of Mediator changes between its recruitment to upstream regulatory regions (enhancers or upstream activating sequences where Mediator is bound to transcription factors) and its action on core promoters together with PIC components.

The functional interplay between Mediator and general transcription factors in PIC assembly is closely related to chromatin architecture at promoter regions.

Direct contact between Mediator and the nuclear pore-associated transcription-coupled export (TREX2) complex suggests that Mediator functions in gene positioning in the nuclear space.

Mediator has been shown to function in the establishment of transcriptional memory, which also involves Mediator interactions with the nuclear pore.

Potential therapeutic targeting and modulation of Mediator activity in cancers and in fungal infectious diseases emphasizes the importance of studies of Mediator mechanisms for improving human health.


Эпигенетический контроль экспрессии генов

While the human genome sequence has transformed our understanding of human biology, it isn’t just the sequence of your DNA that matters, but also how you use it! How are some genes activated and others are silenced? How is this controlled? The answer is epigenetics.

Epigenetics has been a hot topic for research over the past decade as it has become clear that aberrant epigenetic control contributes to disease (particularly to cancer). Epigenetic alterations are heritable through cell division, and in some instances are able to behave similarly to mutations in terms of their stability. Importantly, unlike genetic mutations, epigenetic modifications are reversible and therefore have the potential to be manipulated therapeutically. It has also become clear in recent years that epigenetic modifications are sensitive to the environment (for example diet), which has sparked a large amount of public debate and research. This course will give an introduction to the fundamentals of epigenetic control. We will examine epigenetic phenomena that are manifestations of epigenetic control in several organisms, with a focus on mammals. We will examine the interplay between epigenetic control and the environment and finally the role of aberrant epigenetic control in disease. All necessary information will be covered in the lectures, and recommended and required readings will be provided. There are no additional required texts for this course. For those interested, additional information can be obtained in the following textbook. Epigenetics. Allis, Jenuwein, Reinberg and Caparros. Cold Spring Harbour Laboratory Press. ISBN-13: 978-0879697242 | Edition: 1


References

Roeder, R. G. & Rutter, W. J. Multiple forms of DNA-dependent RNA polymerase in eukaryotic organisms. Nature 224, 234–237 (1969). Fifty years ago, three RNA polymerases were isolated from nuclei of eukaryotic cells.

Sentenac, A. Eukaryotic RNA polymerases. CRC Crit. Rev. Biochem. 18, 31–90 (1985).

Fuda, N. J., Ardehali, M. B. & Lis, J. T. Defining mechanisms that regulate RNA polymerase II transcription in vivo. Nature 461, 186–192 (2009).

Lorch, Y. & Kornberg, R. D. Chromatin-remodeling for transcription. Q. Rev. Biophys. 50, e5 (2017).

Knezetic, J. A. & Luse, D. S. The presence of nucleosomes on a DNA template prevents initiation by RNA polymerase II in vitro. Cell 45, 95–104 (1986).

Lorch, Y., LaPointe, J. W. & Kornberg, R. D. Nucleosomes inhibit the initiation of transcription but allow chain elongation with the displacement of histones. Cell 49, 203–210 (1987).

Talbert, P. B., Meers, M. P. & Henikoff, S. Old cogs, new tricks: the evolution of gene expression in a chromatin context. Nat. Rev. Genet. 20, 283–297 (2019).

Schones, D. E. et al. Dynamic regulation of nucleosome positioning in the human genome. Cell 132, 887–898 (2008).

Müller, F. & Tora, L. Chromatin and DNA sequences in defining promoters for transcription initiation. Biochim. Biophys. Acta 1839, 118–128 (2014).

Vo ngoc, L., Wang, Y. L., Kassavetis, G. A. & Kadonaga, J. T. The punctilious RNA polymerase II core promoter. Genes Dev. 31, 1289–1301 (2017).

Deaton, A. M. & Bird, A. CpG islands and the regulation of transcription. Genes Dev. 25, 1010–1022 (2011).

Schübeler, D. Function and information content of DNA methylation. Nature 517, 321–326 (2015).

Dynan, W. S. & Tjian, R. The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter. Cell 35, 79–87 (1983). Evidence is provided that a DNA sequence-specific transcription factor can guide Pol II to a target promoter.

Engelke, D. R., Ng, S. Y., Shastry, B. S. & Roeder, R. G. Specific interaction of a purified transcription factor with an internal control region of 5S RNA genes. Cell 19, 717–728 (1980). Evidence is provided that a DNA sequence-specific transcription factor can guide Pol III to a target promoter.

Payvar, F. et al. Purified glucocorticoid receptors bind selectively in vitro to a cloned DNA fragment whose transcription is regulated by glucocorticoids in vivo. Proc. Natl Acad. Sci. USA 78, 6628–6632 (1981). A hormone-sensitive DNA sequence-specific transcription factor can bind near its Pol II target promoter.

Mulvihill, E. R., LePennec, J. P. & Chambon, P. Chicken oviduct progesterone receptor: location of specific regions of high-affinity binding in cloned DNA fragments of hormone-responsive genes. Cell 28, 621–632 (1982).

Ptashne, M. & Gann, A. Transcriptional activation by recruitment. Nature 386, 569–577 (1997).

Kadonaga, J. T., Courey, A. J., Ladika, J. & Tjian, R. Distinct regions of Sp1 modulate DNA binding and transcriptional activation. Science 242, 1566–1570 (1988). A transcription factor contains separate DNA binding and transactivation regions.

Sigler, P. B. Acid blobs and negative noodles. Nature 333, 210–212 (1988).

Fong, Y. W., Cattoglio, C., Yamaguchi, T. & Tjian, R. Transcriptional regulation by coactivators in embryonic stem cells. Trends Cell Biol. 22, 292–298 (2012).

Lambert, S. A. et al. The human transcription factors. Cell 172, 650–665 (2018). An inventory of human transcription factors is provided.

Zhu, F. et al. The interaction landscape between transcription factors and the nucleosome. Nature 562, 76–81 (2018).

Iwafuchi-Doi, M. & Zaret, K. S. Cell fate control by pioneer transcription factors. Development 143, 1833–1837 (2016).

Brownell, J. E. et al. Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell 84, 843–851 (1996).

Utley, R. T. et al. Transcriptional activators direct histone acetyltransferase complexes to nucleosomes. Nature 394, 498–502 (1998).

Kraus, W. L. & Kadonaga, J. T. p300 and estrogen receptor cooperatively activate transcription via differential enhancement of initiation and reinitiation. Genes Dev. 12, 331–342 (1998).

An, W., Palhan, V. B., Karymov, M. A., Leuba, S. H. & Roeder, R. G. Selective requirements for histone H3 and H4 N termini in p300-dependent transcriptional activation from chromatin. Mol. Cell 9, 811–821 (2002).

Banerji, J., Rusconi, S. & Schaffner, W. Expression of a β-globin gene is enhanced by remote SV40 DNA sequences. Cell 27, 299–308 (1981).

Benoist, C. & Chambon, P. In vivo sequence requirements of the SV40 early promotor region. Nature 290, 304–310 (1981).

Furlong, E. E. M. & Levine, M. Developmental enhancers and chromosome topology. Science 361, 1341–1345 (2018).

Reiter, F., Wienerroither, S. & Stark, A. Combinatorial function of transcription factors and cofactors. Curr. Opin. Genet. Dev. 43, 73–81 (2017).

Core, L. J. et al. Analysis of nascent RNA identifies a unified architecture of initiation regions at mammalian promoters and enhancers. Nat. Genet. 46, 1311–1320 (2014).

Neil, H. et al. Widespread bidirectional promoters are the major source of cryptic transcripts in yeast. Nature 457, 1038–1042 (2009). Most gene promoters in yeast give rise to bidirectional RNA synthesis.

Robson, M. I., Ringel, A. R. & Mundlos, S. Regulatory landscaping: how enhancer–promoter communication is sculpted in 3D. Mol. Cell 74, 1110–1122 (2019).

van Steensel, B. & Furlong, E. E. M. The role of transcription in shaping the spatial organization of the genome. Nat. Rev. Mol. Cell Biol. 20, 327–337 (2019).

Nora, E. P. et al. Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485, 381–385 (2012).

Sharifi, S. & Bierhoff, H. Regulation of RNA polymerase I transcription in development, disease, and aging. Annu. Rev. Biochem. 87, 51–73 (2018).

Haberle, V. & Stark, A. Eukaryotic core promoters and the functional basis of transcription initiation. Nat. Rev. Mol. Cell Biol. 19, 621–637 (2018).

Dergai, O. & Hernandez, N. How to recruit the correct RNA polymerase? Lessons from snRNA genes. Trends Genet. 35, 457–469 (2019).

Reinberg, D. et al. The RNA polymerase II general transcription factors: past, present, and future. Cold Spring Harb. Symp. Quant. Biol. 63, 83–105 (1998).

Grummt, I. Life on a planet of its own: regulation of RNA polymerase I transcription in the nucleolus. Genes Dev. 17, 1691–1702 (2003

Sentenac, A. & Riva, M. Odd RNA polymerases or the A(B)C of eukaryotic transcription. Biochim. Biophys. Acta 1829, 251–257 (2013).

Schramm, L. & Hernandez, N. Recruitment of RNA polymerase III to its target promoters. Genes Dev. 16, 2593–2620 (2002).

Geiduschek, E. P. & Kassavetis, G. A. The RNA polymerase III transcription apparatus. J. Mol. Biol. 310, 1–26 (2001).

Engel, C. et al. Structural basis of RNA polymerase I transcription initiation. Cell 169, 120–131.e122 (2017). This paper presents the structure of a Pol I pre-initiation complex.

Sadian, Y. et al. Structural insights into transcription initiation by yeast RNA polymerase I. EMBO J. 36, 2698–2709 (2017). This paper presents the structure of a Pol I pre-initiation complex.

Han, Y. et al. Structural mechanism of ATP-independent transcription initiation by RNA polymerase I. eLife 6, e27414 (2017). This paper presents the structure of a Pol I pre-initiation complex.

Schilbach, S. et al. Structures of transcription pre-initiation complex with TFIIH and Mediator. Nature 551, 204–209 (2017). This paper presents the structure of a Pol II pre-initiation complex containing TFIIH and core Mediator.

Plaschka, C. et al. Transcription initiation complex structures elucidate DNA opening. Nature 533, 353–358 (2016).

Plaschka, C. et al. Architecture of the RNA polymerase II–Mediator core initiation complex. Nature 518, 376–380 (2015). The three-dimensional architecture of a Pol II pre-initiation complex containing core Mediator is derived.

Kostrewa, D. et al. RNA polymerase II–TFIIB structure and mechanism of transcription initiation. Nature 462, 323–330 (2009).

Mühlbacher, W. et al. Conserved architecture of the core RNA polymerase II initiation complex. Nat. Commun. 5, 4310 (2014).

Louder, R. K. et al. Structure of promoter-bound TFIID and model of human pre-initiation complex assembly. Nature 531, 604–609 (2016).

He, Y., Fang, J., Taatjes, D. J. & Nogales, E. Structural visualization of key steps in human transcription initiation. Nature 495, 481–486 (2013). This paper describes the architecture of a Pol II pre-initiation complex containing TFIIH.

He, Y. et al. Near-atomic resolution visualization of human transcription promoter opening. Nature 533, 359–365 (2016).

Robinson, P. J. et al. Structure of a complete Mediator–RNA polymerase II pre-initiation complex. Cell 166, 1411–1422.e1416 (2016). This paper describes the overall topology of a Pol II pre-initiation complex containing TFIIH and Mediator.

Liu, X., Bushnell, D. A., Wang, D., Calero, G. & Kornberg, R. D. Structure of an RNA polymerase II–TFIIB complex and the transcription initiation mechanism. Science 327, 206–209 (2010).

Vorländer, M. K., Khatter, H., Wetzel, R., Hagen, W. J. H. & Müller, C. W. Molecular mechanism of promoter opening by RNA polymerase III. Nature 553, 295–300 (2018). The structure of a Pol III pre-initiation complex is described.

Abascal-Palacios, G., Ramsay, E. P., Beuron, F., Morris, E. & Vannini, A. Structural basis of RNA polymerase III transcription initiation. Nature 553, 301–306 (2018). The structure of a Pol III pre-initiation complex is described.

Kornberg, R. D. Eukaryotic transcriptional control. Trends Cell Biol. 9, M46–M49 (1999).

Roeder, R. G. The role of general initiation factors in transcription by RNA polymerase II. Trends Biochem. Sci. 21, 327–335 (1996).

Buratowski, S., Hahn, S., Guarente, L. & Sharp, P. A. Five intermediate complexes in transcription initiation by RNA polymerase II. Cell 56, 549–561 (1989).

Chen, H. T. & Hahn, S. Mapping the location of TFIIB within the RNA polymerase II transcription preinitiation complex: a model for the structure of the PIC. Cell 119, 169–180 (2004).

Bushnell, D. A., Westover, K. D., Davis, R. E. & Kornberg, R. D. Structural basis of transcription: an RNA polymerase II–TFIIB cocrystal at 4.5 angstroms. Science 303, 983–988 (2004).

Sainsbury, S., Niesser, J. & Cramer, P. Structure and function of the initially transcribing RNA polymerase II–TFIIB complex. Nature 493, 437–440 (2013).

Knutson, B. A. & Hahn, S. Yeast Rrn7 and human TAF1B are TFIIB-related RNA polymerase I general transcription factors. Science 333, 1637–1640 (2011).

Vannini, A. & Cramer, P. Conservation between the RNA polymerase I, II, and III transcription initiation machineries. Mol. Cell 45, 439–446 (2012).

Vermeulen, M. et al. Selective anchoring of TFIID to nucleosomes by trimethylation of histone H3 lysine 4. Cell 131, 58–69 (2007).

D’Alessio, J. A., Wright, K. J. & Tjian, R. Shifting players and paradigms in cell-specific transcription. Mol. Cell 36, 924–931 (2009).

Levens, D., Baranello, L. & Kouzine, F. Controlling gene expression by DNA mechanics: emerging insights and challenges. Biophys. Rev. 8, 259–268 (2016).

Pugh, B. F. & Venters, B. J. Genomic organization of human transcription initiation complexes. PLoS ONE 11, e0149339 (2016).

Andersen, P. R., Tirian, L., Vunjak, M. & Brennecke, J. A heterochromatin-dependent transcription machinery drives piRNA expression. Nature 549, 54–59 (2017).

Kassavetis, G. A., Blanco, J. A., Johnson, T. E. & Geiduschek, E. P. Formation of open and elongating transcription complexes by RNA polymerase III. J. Mol. Biol. 226, 47–58 (1992).

Kato, H., Nagamine, M., Kominami, R. & Muramatsu, M. Formation of the transcription initiation complex on mammalian rDNA. Mol. Cell. Biol. 6, 3418–3427 (1986).

Logquist, A. K., Li, H., Imboden, M. A. & Paule, M. R. Promoter opening (melting) and transcription initiation by RNA polymerase I requires neither nucleotide β,γ hydrolysis nor protein phosphorylation. Nucleic Acids Res. 21, 3233–3238 (1993).

Gokal, P. K., Mahajan, P. B. & Thompson, E. A. Hormonal regulation of transcription of rDNA. Formation of initiated complexes by RNA polymerase I in vitro. J. Biol. Chem. 265, 16234–16243 (1990).

Schnapp, A. & Grummt, I. Transcription complex formation at the mouse rDNA promoter involves the stepwise association of four transcription factors and RNA polymerase I. J. Biol. Chem. 266, 24588–24595 (1991).

Feklistov, A. & Darst, S. A. Structural basis for promoter-10 element recognition by the bacterial RNA polymerase σ subunit. Cell 147, 1257–1269 (2011).

Zuo, Y. & Steitz, T. A. Crystal structures of the E. coli transcription initiation complexes with a complete bubble. Mol. Cell 58, 534–540 (2015).

Posse, V. & Gustafsson, C. M. Human mitochondrial transcription factor B2 is required for promoter melting during initiation of transcription. J. Biol. Chem. 292, 2637–2645 (2017).

Hillen, H. S., Morozov, Y. I., Sarfallah, A., Temiakov, D. & Cramer, P. Structural basis of mitochondrial transcription initiation. Cell 171, 1072–1081.e1010 (2017).

Egly, J. M. & Coin, F. A history of TFIIH: two decades of molecular biology on a pivotal transcription/repair factor. DNA Repair (Amst.) 10, 714–721 (2011).

Kim, T. K., Ebright, R. H. & Reinberg, D. Mechanism of ATP-dependent promoter melting by transcription factor IIH. Science 288, 1418–1421 (2000). Crosslinking shows that TFIIH acts on downstream DNA to open the promoter.

Holstege, F. C., van der Vliet, P. C. & Timmers, H. T. Opening of an RNA polymerase II promoter occurs in two distinct steps and requires the basal transcription factors IIE and IIH. EMBO J. 15, 1666–1677 (1996).

Sainsbury, S., Bernecky, C. & Cramer, P. Structural basis of transcription initiation by RNA polymerase II. Nat. Rev. Mol. Cell Biol. 16, 129–143 (2015).

Grünberg, S., Warfield, L. & Hahn, S. Architecture of the RNA polymerase II preinitiation complex and mechanism of ATP-dependent promoter opening. Nat. Struct. Mol. Biol. 19, 788–796 (2012). TFIIH is found to contain a translocase that propels downstream DNA into the Pol II active centre.

Kouzine, F. et al. Global regulation of promoter melting in naive lymphocytes. Cell 153, 988–999 (2013). Promoter DNA opening is a regulated event in cells.

Dienemann, C., Schwalb, B., Schilbach, S. & Cramer, P. Promoter distortion and opening in the RNA polymerase II cleft. Mol. Cell 73, 97–106.e104 (2019).

Alekseev, S. et al. Transcription without XPB establishes a unified helicase-independent mechanism of promoter opening in eukaryotic gene expression. Mol. Cell 65, 504–514.e4 (2017).

Pilsl, M. et al. Structure of the initiation-competent RNA polymerase I and its implication for transcription. Nat. Commun. 7, 12126 (2016).

Blattner, C. et al. Molecular basis of Rrn3-regulated RNA polymerase I initiation and cell growth. Genes Dev. 25, 2093–2105 (2011).

Milkereit, P. & Tschochner, H. A specialized form of RNA polymerase I, essential for initiation and growth-dependent regulation of rRNA synthesis, is disrupted during transcription. EMBO J. 17, 3692–3703 (1998).

Yuan, X., Zhao, J., Zentgraf, H., Hoffmann-Rohrer, U. & Grummt, I. Multiple interactions between RNA polymerase I, TIF-IA and TAFI subunits regulate preinitiation complex assembly at the ribosomal gene promoter. EMBO Rep. 3, 1082–1087 (2002).

Moir, R. D. & Willis, I. M. Regulation of pol III transcription by nutrient and stress signaling pathways. Biochim. Biophys. Acta 1829, 361–375 (2013).

Pluta, K. et al. Maf1p, a negative effector of RNA polymerase III in Saccharomyces cerevisiae. Mol. Cell. Biol. 21, 5031–5040 (2001).

White, R. J. RNA polymerases I and III, non-coding RNAs and cancer. Trends Genet. 24, 622–629 (2008).

Kornberg, R. D. Mediator and the mechanism of transcriptional activation. Trends Biochem. Sci. 30, 235–239 (2005).

Wong, K. H., Jin, Y. & Struhl, K. TFIIH phosphorylation of the Pol II CTD stimulates mediator dissociation from the preinitiation complex and promoter escape. Mol. Cell 54, 601–612 (2014).

Jeronimo, C. & Robert, F. Kin28 regulates the transient association of Mediator with core promoters. Nat. Struct. Mol. Biol. 21, 449–455 (2014).

Tsai, K. L. et al. Mediator structure and rearrangements required for holoenzyme formation. Nature 544, 196–201 (2017).

Nozawa, K., Schneider, T. R. & Cramer, P. Core Mediator structure at 3.4 Å extends model of transcription initiation complex. Nature 545, 248–251 (2017). This paper presents the crystal structure of the core Mediator coactivator complex.

Taatjes, D. J. Transcription factor–mediator interfaces: multiple and multi-valent. J. Mol. Biol. 429, 2996–2998 (2017).

Jeronimo, C. & Robert, F. The mediator complex: at the nexus of RNA Polymerase II transcription. Trends Cell Biol. 27, 765–783 (2017).

Eick, D. & Geyer, M. The RNA polymerase II carboxy-terminal domain (CTD) code. Chem. Rev. 113, 8456–8490 (2013).

Gnatt, A. L., Cramer, P., Fu, J., Bushnell, D. A. & Kornberg, R. D. Structural basis of transcription: an RNA polymerase II elongation complex at 3.3 A resolution. Science 292, 1876–1882 (2001).

Nudler, E. Transcription elongation: structural basis and mechanisms. J. Mol. Biol. 288, 1–12 (1999).

Vassylyev, D. G., Vassylyeva, M. N., Perederina, A., Tahirov, T. H. & Artsimovitch, I. Structural basis for transcription elongation by bacterial RNA polymerase. Nature 448, 157–162 (2007).

Schwinghammer, K. et al. Structure of human mitochondrial RNA polymerase elongation complex. Nat. Struct. Mol. Biol. 20, 1298–1303 (2013).

Neyer, S. et al. Structure of RNA polymerase I transcribing ribosomal DNA genes. Nature 540, 607–610 (2016).

Hoffmann, N. A. et al. Molecular structures of unbound and transcribing RNA polymerase III. Nature 528, 231–236 (2015).

Sidorenkov, I., Komissarova, N. & Kashlev, M. Crucial role of the RNA:DNA hybrid in the processivity of transcription. Mol. Cell 2, 55–64 (1998).

Vassylyev, D. G. et al. Structural basis for substrate loading in bacterial RNA polymerase. Nature 448, 163–168 (2007).

Wang, D., Bushnell, D. A., Westover, K. D., Kaplan, C. D. & Kornberg, R. D. Structural basis of transcription: role of the trigger loop in substrate specificity and catalysis. Cell 127, 941–954 (2006).

Steitz, T. A. & Steitz, J. A. A general two-metal-ion mechanism for catalytic RNA. Proc. Natl Acad. Sci. USA 90, 6498–6502 (1993).

Cramer, P., Bushnell, D. A. & Kornberg, R. D. Structural basis of transcription: RNA polymerase II at 2.8 angstrom resolution. Science 292, 1863–1876 (2001).

Brueckner, F. & Cramer, P. Structural basis of transcription inhibition by α-amanitin and implications for RNA polymerase II translocation. Nat. Struct. Mol. Biol. 15, 811–818 (2008).

Landick, R. The regulatory roles and mechanism of transcriptional pausing. Biochem. Soc. Trans. 34, 1062–1066 (2006).

Conaway, J. W., Shilatifard, A., Dvir, A. & Conaway, R. C. Control of elongation by RNA polymerase II. Trends Biochem. Sci. 25, 375–380 (2000).

Cheung, A. C. & Cramer, P. Structural basis of RNA polymerase II backtracking, arrest and reactivation. Nature 471, 249–253 (2011).

Kuhn, C. D. et al. Functional architecture of RNA polymerase I. Cell 131, 1260–1272 (2007).

Chédin, S., Riva, M., Schultz, P., Sentenac, A. & Carles, C. The RNA cleavage activity of RNA polymerase III is mediated by an essential TFIIS-like subunit and is important for transcription termination. Genes Dev. 12, 3857–3871 (1998).

Bentley, D. L. & Groudine, M. A block to elongation is largely responsible for decreased transcription of c-myc in differentiated HL60 cells. Nature 321, 702–706 (1986).

Eick, D. & Bornkamm, G. W. Transcriptional arrest within the first exon is a fast control mechanism in c-myc gene expression. Nucleic Acids Res. 14, 8331–8346 (1986).

Gariglio, P., Bellard, M. & Chambon, P. Clustering of RNA polymerase B molecules in the 5′ moiety of the adult β-globin gene of hen erythrocytes. Nucleic Acids Res. 9, 2589–2598 (1981).

Rougvie, A. E. & Lis, J. T. The RNA polymerase II molecule at the 5′ end of the uninduced hsp70 gene of D. melanogaster is transcriptionally engaged. Cell 54, 795–804 (1988).

Strobl, L. J. & Eick, D. Hold back of RNA polymerase II at the transcription start site mediates down-regulation of c-myc in vivo. EMBO J. 11, 3307–3314 (1992).

Tome, J. M., Tippens, N. D. & Lis, J. T. Single-molecule nascent RNA sequencing identifies regulatory domain architecture at promoters and enhancers. Nat. Genet. 50, 1533–1541 (2018).

Core, L. & Adelman, K. Promoter-proximal pausing of RNA polymerase II: a nexus of gene regulation. Genes Dev. https://doi.org/10.1101/gad.325142.119 (2019).

Vos, S. M., Farnung, L., Urlaub, H. & Cramer, P. Structure of paused transcription complex Pol II–DSIF–NELF. Nature 560, 601–606 (2018).

Kang, J. Y. et al. Structural basis for transcript elongation control by NusG family universal regulators. Cell 173, 1650–1662.e1614 (2018).

Guo, X. et al. Structural basis for NusA stabilized transcriptional pausing. Mol. Cell 69, 816–827.e814 (2018).

Saba, J. et al. The elemental mechanism of transcriptional pausing. eLife 8, e40981 (2019).

Yamaguchi, Y., Shibata, H. & Handa, H. Transcription elongation factors DSIF and NELF: promoter-proximal pausing and beyond. Biochim. Biophys. Acta 1829, 98–104 (2013).

Bernecky, C., Plitzko, J. M. & Cramer, P. Structure of a transcribing RNA polymerase II–DSIF complex reveals a multidentate DNA–RNA clamp. Nat. Struct. Mol. Biol. 24, 809–815 (2017).

Ehara, H. et al. Structure of the complete elongation complex of RNA polymerase II with basal factors. Science 357, 921–924 (2017).

Palangat, M., Renner, D. B., Price, D. H. & Landick, R. A negative elongation factor for human RNA polymerase II inhibits the anti-arrest transcript-cleavage factor TFIIS. Proc. Natl Acad. Sci. USA 102, 15036–15041 (2005).

Kettenberger, H., Armache, K. J. & Cramer, P. Architecture of the RNA polymerase II–TFIIS complex and implications for mRNA cleavage. Cell 114, 347–357 (2003).

Vos, S. M. et al. Structure of activated transcription complex Pol II–DSIF–PAF–SPT6. Nature 560, 607–612 (2018). The structure of a mammalian, activated Pol II elongation complex provides a model for polymerase release from promoter-proximal pausing.

Marshall, N. F. & Price, D. H. Purification of P-TEFb, a transcription factor required for the transition into productive elongation. J. Biol. Chem. 270, 12335–12338 (1995).

Zhou, Q., Li, T. & Price, D. H. RNA polymerase II elongation control. Annu. Rev. Biochem. 81, 119–143 (2012).

Kwak, H. & Lis, J. T. Control of transcriptional elongation. Annu. Rev. Genet. 47, 483–508 (2013).

Sdano, M. A. et al. A novel SH2 recognition mechanism recruits Spt6 to the doubly phosphorylated RNA polymerase II linker at sites of transcription. eLife 6, e28723 (2017).

Van Oss, S. B., Cucinotta, C. E. & Arndt, K. M. Emerging insights into the roles of the Paf1 complex in gene regulation. Trends Biochem. Sci. 42, 788–798 (2017).

Shao, W. & Zeitlinger, J. Paused RNA polymerase II inhibits new transcriptional initiation. Nat. Genet. 49, 1045–1051 (2017). Evidence is presented that promoter-proximal pausing can regulate transcription by suppressing initiation.

Gressel, S. et al. CDK9-dependent RNA polymerase II pausing controls transcription initiation. eLife 6, e29736 (2017). Evidence is presented that promoter-proximal pausing can regulate transcription initiation.

Ehrensberger, A. H., Kelly, G. P. & Svejstrup, J. Q. Mechanistic interpretation of promoter-proximal peaks and RNAPII density maps. Cell 154, 713–715 (2013).

Brown, S. A., Weirich, C. S., Newton, E. M. & Kingston, R. E. Transcriptional activation domains stimulate initiation and elongation at different times and via different residues. EMBO J. 17, 3146–3154 (1998).

Rahl, P. B. et al. c-Myc regulates transcriptional pause release. Cell 141, 432–445 (2010). A transcription factor can regulate transcription elongation.

Li, Y., Liu, M., Chen, L. F. & Chen, R. P-TEFb: Finding its ways to release promoter-proximally paused RNA polymerase II. Transcription 9, 88–94 (2018).

Smith, E., Lin, C. & Shilatifard, A. The super elongation complex (SEC) and MLL in development and disease. Genes Dev. 25, 661–672 (2011).

Sobhian, B. et al. HIV-1 Tat assembles a multifunctional transcription elongation complex and stably associates with the 7SK snRNP. Mol. Cell 38, 439–451 (2010).

Yang, Z., Zhu, Q., Luo, K. & Zhou, Q. The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription. Nature 414, 317–322 (2001).

Nguyen, V. T., Kiss, T., Michels, A. A. & Bensaude, O. 7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes. Nature 414, 322–325 (2001).

Buratowski, S. Progression through the RNA polymerase II CTD cycle. Mol. Cell 36, 541–546 (2009).

Bentley, D. L. Coupling mRNA processing with transcription in time and space. Nat. Rev. Genet. 15, 163–175 (2014).

Shilatifard, A., Conaway, R. C. & Conaway, J. W. The RNA polymerase II elongation complex. Annu. Rev. Biochem. 72, 693–715 (2003).

Becker, P. B. & Workman, J. L. Nucleosome remodeling and epigenetics. Cold Spring Harb. Perspect. Biol. 5, a017905 (2013).

Clapier, C. R., Iwasa, J., Cairns, B. R. & Peterson, C. L. Mechanisms of action and regulation of ATP-dependent chromatin-remodelling complexes. Nat. Rev. Mol. Cell Biol. 18, 407–422 (2017).

Chen, F. X., Smith, E. R. & Shilatifard, A. Born to run: control of transcription elongation by RNA polymerase II. Nat. Rev. Mol. Cell Biol. 19, 464–478 (2018).

Shilatifard, A. The COMPASS family of histone H3K4 methylases: mechanisms of regulation in development and disease pathogenesis. Annu. Rev. Biochem. 81, 65–95 (2012).

McDaniel, S. L. & Strahl, B. D. Shaping the cellular landscape with Set2/SETD2 methylation. Cell. Mol. Life Sci. 74, 3317–3334 (2017).

French, C. A. Small-molecule targeting of BET proteins in cancer. Adv. Cancer Res. 131, 21–58 (2016).

Bradner, J. E., Hnisz, D. & Young, R. A. Transcriptional addiction in cancer. Cell 168, 629–643 (2017).

Ditlev, J. A., Case, L. B. & Rosen, M. K. Who’s in and who’s out–compositional control of biomolecular condensates. J. Mol. Biol. 430, 4666–4684 (2018).

Tolhuis, B., Palstra, R. J., Splinter, E., Grosveld, F. & de Laat, W. Looping and interaction between hypersensitive sites in the active β-globin locus. Mol. Cell 10, 1453–1465 (2002).

Papantonis, A. & Cook, P. R. Transcription factories: genome organization and gene regulation. Chem. Rev. 113, 8683–8705 (2013).

Cisse, I. I. et al. Real-time dynamics of RNA polymerase II clustering in live human cells. Science 341, 664–667 (2013). Live-cell imaging visualizes Pol II clusters and their dynamics in human nuclei.

Buckley, M. S. & Lis, J. T. Imaging RNA polymerase II transcription sites in living cells. Curr. Opin. Genet. Dev. 25, 126–130 (2014).

Cho, W. K. et al. Mediator and RNA polymerase II clusters associate in transcription-dependent condensates. Science 361, 412–415 (2018). Imaging reveals nuclear condensates for Pol II transcription.

Chong, S. et al. Imaging dynamic and selective low-complexity domain interactions that control gene transcription. Science 361, eaar2555 (2018). Imaging reveals nuclear condensates for Pol II transcription.

Sabari, B. R. et al. Coactivator condensation at super-enhancers links phase separation and gene control. Science 361, eaar3958 (2018). Imaging reveals nuclear condensates for Pol II transcription.

Boehning, M. et al. RNA polymerase II clustering through carboxy-terminal domain phase separation. Nat. Struct. Mol. Biol. 25, 833–840 (2018). Imaging reveals nuclear condensates for Pol II transcription.

Hnisz, D., Shrinivas, K., Young, R. A., Chakraborty, A. K. & Sharp, P. A. A phase separation model for transcriptional control. Cell 169, 13–23 (2017). This article presents the hypothesis that transcription involves phase-separated nuclear condensates.

Boija, A. et al. Transcription factors activate genes through the phase-separation capacity of their activation domains. Cell 175, 1842–1855.e1816 (2018).

Nair, S. J. et al. Phase separation of ligand-activated enhancers licenses cooperative chromosomal enhancer assembly. Nat. Struct. Mol. Biol. 26, 193–203 (2019).

Kato, M. & McKnight, S. L. A solid-state conceptualization of information transfer from gene to message to protein. Annu. Rev. Biochem. 87, 351–390 (2018).

Banani, S. F., Lee, H. O., Hyman, A. A. & Rosen, M. K. Biomolecular condensates: organizers of cellular biochemistry. Nat. Rev. Mol. Cell Biol. 18, 285–298 (2017).

Kwon, I. et al. Phosphorylation-regulated binding of RNA polymerase II to fibrous polymers of low-complexity domains. Cell 155, 1049–1060 (2013).

Lu, F., Portz, B. & Gilmour, D. S. The C-terminal domain of RNA polymerase II is a multivalent targeting sequence that supports Drosophila development with only consensus heptads. Mol. Cell 73, 1232–1242.e1234 (2019).

Lu, H. et al. Phase-separation mechanism for C-terminal hyperphosphorylation of RNA polymerase II. Nature 558, 318–323 (2018).

Herzel, L., Ottoz, D. S. M., Alpert, T. & Neugebauer, K. M. Splicing and transcription touch base: co-transcriptional spliceosome assembly and function. Nat. Rev. Mol. Cell Biol. 18, 637–650 (2017).

Bregman, D. B., Du, L., van der Zee, S. & Warren, S. L. Transcription-dependent redistribution of the large subunit of RNA polymerase II to discrete nuclear domains. J. Cell Biol. 129, 287–298 (1995).

Mortillaro, M. J. et al. A hyperphosphorylated form of the large subunit of RNA polymerase II is associated with splicing complexes and the nuclear matrix. Proc. Natl Acad. Sci. USA 93, 8253–8257 (1996).

Misteli, T. & Spector, D. L. RNA polymerase II targets pre-mRNA splicing factors to transcription sites in vivo. Mol. Cell 3, 697–705 (1999).

Van Treeck, B. & Parker, R. Emerging roles for intermolecular RNA–RNA interactions in RNP assemblies. Cell 174, 791–802 (2018).

Battaglia, S. et al. RNA-dependent chromatin association of transcription elongation factors and Pol II CTD kinases. eLife 6, e25637 (2017).

Lewis, J. D. & Tollervey, D. Like attracts like: getting RNA processing together in the nucleus. Science 288, 1385–1389 (2000).

Molliex, A. et al. Phase separation by low complexity domains promotes stress granule assembly and drives pathological fibrillization. Cell 163, 123–133 (2015).

Castello, A. et al. Comprehensive identification of RNA-binding domains in human cells. Mol. Cell 63, 696–710 (2016).

Ghamari, A. et al. In vivo live imaging of RNA polymerase II transcription factories in primary cells. Genes Dev. 27, 767–777 (2013).

Proudfoot, N. J. Transcriptional termination in mammals: stopping the RNA polymerase II juggernaut. Science 352, aad9926 (2016).

Parua, P. K. et al. A Cdk9–PP1 switch regulates the elongation–termination transition of RNA polymerase II. Nature 558, 460–464 (2018).

Fukaya, T., Lim, B. & Levine, M. Enhancer control of transcriptional bursting. Cell 166, 358–368 (2016). An enhancer is shown to be able to activate two target genes.

Kamieniarz-Gdula, K. & Proudfoot, N. J. Transcriptional control by premature termination: a forgotten mechanism. Trends Genet. 35, 553–564 (2019).

Porrua, O., Boudvillain, M. & Libri, D. Transcription termination: variations on common themes. Trends Genet. 32, 508–522 (2016).

Gibson, B. A. et al. Organization and regulation of chromatin by liquid–liquid phase separation. Preprint at https://www.biorxiv.org/content/10.1101/523662v1 (2019).Histones are shown to undergo phase separation.

Farnung, L., Vos, S. M. & Cramer, P. Structure of transcribing RNA polymerase II–nucleosome complex. Nat. Commun. 9, 5432 (2018). Cryo-electron microscopy provides the structure of a Pol II–nucleosome complex.

Ehara, H. et al. Structural insight into nucleosome transcription by RNA polymerase II with elongation factors. Science 363, 744–747 (2019).

Kujirai, T. et al. Structural basis of the nucleosome transition during RNA polymerase II passage. Science 362, 595–598 (2018). Cryo-electron microscopy provides the structures of several Pol II–nucleosome complexes.

Skene, P. J., Hernandez, A. E., Groudine, M. & Henikoff, S. The nucleosomal barrier to promoter escape by RNA polymerase II is overcome by the chromatin remodeler Chd1. eLife 3, e02042 (2014).

Smolle, M. et al. Chromatin remodelers Isw1 and Chd1 maintain chromatin structure during transcription by preventing histone exchange. Nat. Struct. Mol. Biol. 19, 884–892 (2012).

Hsieh, F. K. et al. Histone chaperone FACT action during transcription through chromatin by RNA polymerase II. Proc. Natl Acad. Sci. USA 110, 7654–7659 (2013).

Orphanides, G., LeRoy, G., Chang, C. H., Luse, D. S. & Reinberg, D. FACT, a factor that facilitates transcript elongation through nucleosomes. Cell 92, 105–116 (1998).

Guo, Y. E. et al. Pol II phosphorylation regulates a switch between transcriptional and splicing condensates. Nature 572, 543–548 (2019).

Chen, F., Gao, X. & Shilatifard, A. Stably paused genes revealed through inhibition of transcription initiation by the TFIIH inhibitor triptolide. Genes Dev. 29, 39–47 (2015).

Titov, D. V. et al. XPB, a subunit of TFIIH, is a target of the natural product triptolide. Nat. Chem. Biol. 7, 182–188 (2011).

Bensaude, O. Inhibiting eukaryotic transcription: which compound to choose? How to evaluate its activity? Transcription 2, 103–108 (2011).

Kwiatkowski, N. et al. Targeting transcription regulation in cancer with a covalent CDK7 inhibitor. Nature 511, 616–620 (2014).

Chao, S. H. et al. Flavopiridol inhibits P-TEFb and blocks HIV-1 replication. J. Biol. Chem. 275, 28345–28348 (2000).

Zhu, Y. et al. Transcription elongation factor P-TEFb is required for HIV-1 tat transactivation in vitro. Genes Dev. 11, 2622–2632 (1997).

Jeruzalmi, D. & Steitz, T. A. Structure of T7 RNA polymerase complexed to the transcriptional inhibitor T7 lysozyme. EMBO J. 17, 4101–4113 (1998).

Hillen, H. S., Temiakov, D. & Cramer, P. Structural basis of mitochondrial transcription. Nat. Struct. Mol. Biol. 25, 754–765 (2018).

Zhang, G. et al. Crystal structure of Thermus aquaticus core RNA polymerase at 3.3 Å resolution. Cell 98, 811–824 (1999).

Nudler, E. RNA polymerase active center: the molecular engine of transcription. Annu. Rev. Biochem. 78, 335–361 (2009).

Ray-Soni, A., Bellecourt, M. J. & Landick, R. Mechanisms of bacterial transcription termination: all good things must end. Annu. Rev. Biochem. 85, 319–347 (2016).

Feng, Y., Zhang, Y. & Ebright, R. H. Structural basis of transcription activation. Science 352, 1330–1333 (2016).

Martinez-Rucobo, F. W. & Cramer, P. Structural basis of transcription elongation. Biochim. Biophys. Acta 1829, 9–19 (2013).

Nogales, E., Patel, A. B. & Louder, R. K. Towards a mechanistic understanding of core promoter recognition from cryo-EM studies of human TFIID. Curr. Opin. Struct. Biol. 47, 60–66 (2017).

Khatter, H., Vorländer, M. K. & Müller, C. W. RNA polymerase I and III: similar yet unique. Curr. Opin. Struct. Biol. 47, 88–94 (2017).

Kornberg, R. D. The molecular basis of eukaryotic transcription. Proc. Natl Acad. Sci. USA 104, 12955–12961 (2007).

Engel, C., Neyer, S. & Cramer, P. distinct mechanisms of transcription initiation by RNA polymerases I and II. Annu. Rev. Biophys. 47, 425–446 (2018).

Bieniossek, C. et al. The architecture of human general transcription factor TFIID core complex. Nature 493, 699–702 (2013).

Cramer, P. et al. Architecture of RNA polymerase II and implications for the transcription mechanism. Science 288, 640–649 (2000).

Engel, C., Sainsbury, S., Cheung, A. C., Kostrewa, D. & Cramer, P. RNA polymerase I structure and transcription regulation. Nature 502, 650–655 (2013).

Fernández-Tornero, C. et al. Crystal structure of the 14-subunit RNA polymerase I. Nature 502, 644–649 (2013).

Jasiak, A. J., Armache, K. J., Martens, B., Jansen, R. P. & Cramer, P. Structural biology of RNA polymerase III: subcomplex C17/25 X-ray structure and 11 subunit enzyme model. Mol. Cell 23, 71–81 (2006).

Werner, F. & Grohmann, D. Evolution of multisubunit RNA polymerases in the three domains of life. Nat. Rev. Microbiol. 9, 85–98 (2011).

Haag, J. R. & Pikaard, C. S. Multisubunit RNA polymerases IV and V: purveyors of non-coding RNA for plant gene silencing. Nat. Rev. Mol. Cell Biol. 12, 483–492 (2011).


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