There are numerous data suggesting that two key steps in gene expression-transcription and splicing influence each other closely. For a long time it was known that chromatin modifications regulate transcription, but only recently it was shown that chromatin and histone modifications play a significant role in pre-mRNA splicing. Here we summarize interactions between splicing machinery and chromatin and discuss their potential functional significance. We focus mainly on histone acetylation and methylation and potential mechanisms of their role in splicing. It seems that whereas histone acetylation acts mainly by alterating the transcription rate, histone methylation can also influence splicing directly by recruiting various splicing components.

Department of RNA Biology Institute of Molecular Genetics Academy of Sciences of the Czech Republic Prague

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Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409:860–921. PubMed

Scherer S. A short guide to the human genome. Cold Spring Harbor NY: Cold Spring Harbor Laboratory Press; 2008. p. 34.

Wang ET, Sandberg R, Luo S, Khrebtukova I, Zhang L, Mayr C. Alternative isoform regulation in human tissue transcriptomes. Nature. 2008;456:470–476. PubMed PMC

Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat Genet. 2008;40:1413–1415. PubMed

Wang Z, Burge CB. Splicing regulation: from a parts list of regulatory elements to an integrated splicing code. RNA. 2008;14:802–813. PubMed PMC

Black DL. Mechanisms of alternative pre-messenger RNA splicing. Annu Rev Biochem. 2003;72:291–336. PubMed

Barash Y, Calarco JA, Gao W, Pan Q, Wang X, Shai O, et al. Deciphering the splicing code. Nature. 2010;465:53–59. PubMed

Singh J, Padgett RA. Rates of in situ transcription and splicing in large human genes. Nat Struct Mol Biol. 2009;16:1128–1133. PubMed PMC

Tennyson CN, Klamut HJ, Worton RG. The human dystrophin gene requires 16 hours to be transcribed and is cotranscriptionally spliced. Nat Genet. 1995;9:184–190. PubMed

Pandya-Jones A, Black DL. Co-transcriptional splicing of constitutive and alternative exons. RNA. 2009;15:1896–1908. PubMed PMC

Listerman I, Sapra AK, Neugebauer KM. Cotranscriptional coupling of splicing factor recruitment and precursor messenger RNA splicing in mammalian cells. Nat Struct Mol Biol. 2006;13:815–822. PubMed

Zhang G, Taneja KL, Singer RH, Green MR. Localization of pre-mRNA splicing in mammalian nuclei. Nature. 1994;372:809–812. PubMed

Bauren G, Wieslander L. Splicing of Balbiani ring 1 gene pre-mRNA occurs simultaneously with transcription. Cell. 1994;76:183–192. PubMed

Wada Y, Ohta Y, Xu M, Tsutsumi S, Minami T, Inoue K, et al. A wave of nascent transcription on activated human genes. Proc Natl Acad Sci USA. 2009;106:18357–18361. PubMed PMC

Bittencourt D, Dutertre M, Sanchez G, Barbier J, Gratadou L, Auboeuf D. Cotranscriptional splicing potentiates the mRNA production from a subset of estradiol-stimulated genes. Mol Cell Biol. 2008;28:5811–5824. PubMed PMC

Carrillo Oesterreich F, Preibisch S, Neugebauer KM. Global analysis of nascent RNA reveals transcriptional pausing in terminal exons. Mol Cell. 2010;40:571–581. PubMed

Lacadie SA, Rosbash M. Cotranscriptional spliceosome assembly dynamics and the role of U1 snRNA:5′ss base pairing in yeast. Mol Cell. 2005;19:65–75. PubMed

Gornemann J, Kotovic KM, Hujer K, Neugebauer KM. Cotranscriptional spliceosome assembly occurs in a stepwise fashion and requires the cap binding complex. Mol Cell. 2005;19:53–63. PubMed

Lacadie SA, Tardiff DF, Kadener S, Rosbash M. In vivo commitment to yeast cotranscriptional splicing is sensitive to transcription elongation mutants. Genes Dev. 2006;20:2055–2066. PubMed PMC

Alexander RD, Barrass JD, Dichtl B, Kos M, Obtulowicz T, Robert MC, et al. RiboSys, a high-resolution, quantitative approach to measure the in vivo kinetics of pre-mRNA splicing and 3′-end processing in Saccharomyces cerevisiae. RNA. 2010;16:2570–2580. PubMed PMC

Alexander RD, Innocente SA, Barrass JD, Beggs JD. Splicing-dependent RNA polymerase pausing in yeast. Mol Cell. 2010;40:582–593. PubMed PMC

Auboeuf D, Honig A, Berget SM, O'Malley BW. Coordinate regulation of transcription and splicing by steroid receptor coregulators. Science. 2002;298:416–419. PubMed

Kadener S, Cramer P, Nogues G, Cazalla D, de la Mata M, Fededa JP, et al. Antagonistic effects of T-Ag and VP16 reveal a role for RNA pol II elongation on alternative splicing. EMBO J. 2001;20:5759–5768. PubMed PMC

Kadener S, Fededa JP, Rosbash M, Kornblihtt AR. Regulation of alternative splicing by a transcriptional enhancer through RNA pol II elongation. Proc Natl Acad Sci USA. 2002;99:8185–8190. PubMed PMC

Kornblihtt AR. Promoter usage and alternative splicing. Curr Opin Cell Biol. 2005;17:262–268. PubMed

Moldon A, Malapeira J, Gabrielli N, Gogol M, Gomez-Escoda B, Ivanova T, et al. Promoter-driven splicing regulation in fission yeast. Nature. 2008;455:997–1000. PubMed

Cramer P, Caceres JF, Cazalla D, Kadener S, Muro AF, Baralle FE, et al. Coupling of transcription with alternative splicing: RNA pol II promoters modulate SF2/ASF and 9G8 effects on an exonic splicing enhancer. Mol Cell. 1999;4:251–258. PubMed

Cramer P, Pesce CG, Baralle FE, Kornblihtt AR. Functional association between promoter structure and transcript alternative splicing. Proc Natl Acad Sci USA. 1997;94:11456–11460. PubMed PMC

Pagani F, Stuani C, Zuccato E, Kornblihtt AR, Baralle FE. Promoter architecture modulates CFTR exon 9 skipping. J Biol Chem. 2003;278:1511–1517. PubMed

Auboeuf D, Dowhan DH, Li X, Larkin K, Ko L, Berget SM, et al. CoAA, a nuclear receptor coactivator protein at the interface of transcriptional coactivation and RNA splicing. Mol Cell Biol. 2004;24:442–453. PubMed PMC

Auboeuf D, Dowhan DH, Kang YK, Larkin K, Lee JW, Berget SM, et al. Differential recruitment of nuclear receptor coactivators may determine alternative RNA splice site choice in target genes. Proc Natl Acad Sci USA. 2004;101:2270–2274. PubMed PMC

Rosonina E, Bakowski MA, McCracken S, Blencowe BJ. Transcriptional activators control splicing and 3′-end cleavage levels. J Biol Chem. 2003;278:43034–43040. PubMed

Monsalve M, Wu Z, Adelmant G, Puigserver P, Fan M, Spiegelman BM. Direct coupling of transcription and mRNA processing through the thermogenic coactivator PGC-1. Mol Cell. 2000;6:307–316. PubMed

Munoz MJ, Perez Santangelo MS, Paronetto MP, de la Mata M, Pelisch F, Boireau S, et al. DNA damage regulates alternative splicing through inhibition of RNA polymerase II elongation. Cell. 2009;137:708–720. PubMed

de la Mata M, Alonso CR, Kadener S, Fededa JP, Blaustein M, Pelisch F, et al. A slow RNA polymerase II affects alternative splicing in vivo. Mol Cell. 2003;12:525–532. PubMed

Nogues G, Kadener S, Cramer P, Bentley D, Kornblihtt AR. Transcriptional activators differ in their abilities to control alternative splicing. J Biol Chem. 2002;277:43110–43114. PubMed

Ip JY, Schmidt D, Pan Q, Ramani AK, Fraser AG, Odom DT, et al. Global impact of RNA polymerase II elongation inhibition on alternative splicing regulation. Genome Res. 2011;21:390–401. PubMed PMC

Hnilicova J, Hozeifi S, Duskova E, Icha J, Tomankova T, Stanek D. Histone deacetylase activity modulates alternative splicing. PLoS One. 2011;6:16727. PubMed PMC

Batsche E, Yaniv M, Muchardt C. The human SWI/SNF subunit Brm is a regulator of alternative splicing. Nat Struct Mol Biol. 2006;13:22–29. PubMed

Allo M, Buggiano V, Fededa JP, Petrillo E, Schor I, de la Mata M, et al. Control of alternative splicing through siRNA-mediated transcriptional gene silencing. Nat Struct Mol Biol. 2009;16:717–724. PubMed

Howe KJ, Kane CM, Ares M., Jr Perturbation of transcription elongation influences the fidelity of internal exon inclusion in Saccharomyces cerevisiae. RNA. 2003;9:993–1006. PubMed PMC

Roberts GC, Gooding C, Mak HY, Proudfoot NJ, Smith CW. Co-transcriptional commitment to alternative splice site selection. Nucleic Acids Res. 1998;26:5568–5572. PubMed PMC

Nogues G, Munoz MJ, Kornblihtt AR. Influence of polymerase II processivity on alternative splicing depends on splice site strength. J Biol Chem. 2003;278:52166–52171. PubMed

de la Mata M, Kornblihtt AR. RNA polymerase II C-terminal domain mediates regulation of alternative splicing by SRp20. Nat Struct Mol Biol. 2006;13:973–980. PubMed

Barboric M, Lenasi T, Chen H, Johansen EB, Guo S, Peterlin BM. 7SK snRNP/P-TEFb couples transcription elongation with alternative splicing and is essential for vertebrate development. Proc Natl Acad Sci USA. 2009;106:7798–7803. PubMed PMC

Darzacq X, Shav-Tal Y, de Turris V, Brody Y, Shenoy SM, Phair RD, et al. In vivo dynamics of RNA polymerase II transcription. Nat Struct Mol Biol. 2007;14:796–806. PubMed PMC

Boireau S, Maiuri P, Basyuk E, de la Mata M, Knezevich A, Pradet-Balade B, et al. The transcriptional cycle of HIV-1 in real-time and live cells. J Cell Biol. 2007;179:291–304. PubMed PMC

Mason PB, Struhl K. Distinction and relationship between elongation rate and processivity of RNA polymerase II in vivo. Mol Cell. 2005;17:831–840. PubMed

Ben-Ari Y, Brody Y, Kinor N, Mor A, Tsukamoto T, Spector DL, et al. The life of an mRNA in space and time. J Cell Sci. 2010;123:1761–1774. PubMed PMC

Huranova M, Ivani I, Benda A, Poser I, Brody Y, Hof M, et al. The differential interaction of snRNPs with pre-mRNA reveals splicing kinetics in living cells. J Cell Biol. 2010;191:75–86. PubMed PMC

Wetterberg I, Zhao J, Masich S, Wieslander L, Skoglund U. In situ transcription and splicing in the Balbiani ring 3 gene. EMBO J. 2001;20:2564–2574. PubMed PMC

Kouzarides T. Chromatin modifications and their function. Cell. 2007;128:693–705. PubMed

Radman-Livaja M, Rando OJ. Nucleosome positioning: how is it established and why does it matter? Dev Biol. 2009;339:258–266. PubMed PMC

Kolasinska-Zwierz P, Down T, Latorre I, Liu T, Liu XS, Ahringer J. Differential chromatin marking of introns and expressed exons by H3K36me3. Nat Genet. 2009;41:376–381. PubMed PMC

Schwartz S, Meshorer E, Ast G. Chromatin organization marks exon-intron structure. Nat Struct Mol Biol. 2009;16:990–995. PubMed

Tilgner H, Nikolaou C, Althammer S, Sammeth M, Beato M, Valcarcel J, et al. Nucleosome positioning as a determinant of exon recognition. Nat Struct Mol Biol. 2009;16:996–1001. PubMed

Andersson R, Enroth S, Rada-Iglesias A, Wadelius C, Komorowski J. Nucleosomes are well positioned in exons and carry characteristic histone modifications. Genome Res. 2009;19:1732–1741. PubMed PMC

Dhami P, Saffrey P, Bruce AW, Dillon SC, Chiang K, Bonhoure N, et al. Complex exon-intron marking by histone modifications is not determined solely by nucleosome distribution. PLoS One. 2009;5:12339. PubMed PMC

Spies N, Nielsen CB, Padgett RA, Burge CB. Biased chromatin signatures around polyadenylation sites and exons. Mol Cell. 2009;36:245–254. PubMed PMC

Huff JT, Plocik AM, Guthrie C, Yamamoto KR. Reciprocal intronic and exonic histone modification regions in humans. Nat Struct Mol Biol. 2010;17:1495–1499. PubMed PMC

Hon G, Wang W, Ren B. Discovery and annotation of functional chromatin signatures in the human genome. PLoS Comput Biol. 2009;5:1000566. PubMed PMC

Nahkuri S, Taft RJ, Mattick JS. Nucleosomes are preferentially positioned at exons in somatic and sperm cells. Cell Cycle. 2009;8:3420–3424. PubMed

Schwartz S, Ast G. Chromatin density and splicing destiny: on the cross-talk between chromatin structure and splicing. EMBO J. 2010;29:1629–1636. PubMed PMC

Tilgner H, Guigo R. From chromatin to splicing: RNA-processing as a total artwork. Epigenetics. 2010:5. PubMed

Loomis RJ, Naoe Y, Parker JB, Savic V, Bozovsky MR, Macfarlan T, et al. Chromatin binding of SRp20 and ASF/SF2 and dissociation from mitotic chromosomes is modulated by histone H3 serine 10 phosphorylation. Mol Cell. 2009;33:450–461. PubMed PMC

Barth TK, Imhof A. Fast signals and slow marks: the dynamics of histone modifications. Trends Biochem Sci. 2010;35:618–626. PubMed

Schor IE, Rascovan N, Pelisch F, Allo M, Kornblihtt AR. Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing. Proc Natl Acad Sci USA. 2009;106:4325–4330. PubMed PMC

Gunderson FQ, Johnson TL. Acetylation by the transcriptional coactivator Gcn5 plays a novel role in co-transcriptional spliceosome assembly. PLoS Genet. 2009;5:1000682. PubMed PMC

Gunderson FQ, Merkhofer EC, Johnson TL. Dynamic histone acetylation is critical for cotranscriptional spliceosome assembly and spliceosomal rearrangements. Proc Natl Acad Sci USA. 2011;108:2004–2009. PubMed PMC

Kotovic KM, Lockshon D, Boric L, Neugebauer KM. Cotranscriptional recruitment of the U1 snRNP to intron-containing genes in yeast. Mol Cell Biol. 2003;23:5768–5779. PubMed PMC

Konarska MM, Sharp PA. Electrophoretic separation of complexes involved in the splicing of precursors to mRNAs. Cell. 1986;46:845–855. PubMed

Bindereif A, Green MR. An ordered pathway of snRNP binding during mammalian pre-mRNA splicing complex assembly. EMBO J. 1987;6:2415–2424. PubMed PMC

Jurica MS, Licklider LJ, Gygi SR, Grigorieff N, Moore MJ. Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis. RNA. 2002;8:426–439. PubMed PMC

Tardiff DF, Rosbash M. Arrested yeast splicing complexes indicate stepwise snRNP recruitment during in vivo spliceosome assembly. RNA. 2006;12:968–979. PubMed PMC

Tardiff DF, Lacadie SA, Rosbash M. A genome-wide analysis indicates that yeast pre-mRNA splicing is predominantly posttranscriptional. Mol Cell. 2006;24:917–929. PubMed PMC

Wahl MC, Will CL, Luhrmann R. The spliceosome: design principles of a dynamic RNP machine. Cell. 2009;136:701–718. PubMed

Jobert L, Pinzon N, Van Herreweghe E, Jady BE, Guialis A, Kiss T, et al. Human U1 snRNA forms a new chromatin-associated snRNP with TAF15. EMBO Rep. 2009;10:494–500. PubMed PMC

Damgaard CK, Kahns S, Lykke-Andersen S, Nielsen AL, Jensen TH, Kjems J. A 5′ splice site enhances the recruitment of basal transcription initiation factors in vivo. Mol Cell. 2008;29:271–278. PubMed

Kwek KY, Murphy S, Furger A, Thomas B, O'Gorman W, Kimura H, et al. U1 snRNA associates with TFIIH and regulates transcriptional initiation. Nat Struct Biol. 2002;9:800–805. PubMed

O'Gorman W, Thomas B, Kwek KY, Furger A, Akoulitchev A. Analysis of U1 small nuclear RNA interaction with cyclin H. J Biol Chem. 2005;280:36920–36925. PubMed

Ares M, Jr, Grate L, Pauling MH. A handful of intron-containing genes produces the lion's share of yeast mRNA. RNA. 1999;5:1138–1139. PubMed PMC

Furger A, O'Sullivan JM, Binnie A, Lee BA, Proudfoot NJ. Promoter proximal splice sites enhance transcription. Genes Dev. 2002;16:2792–2799. PubMed PMC

Eberle AB, Hessle V, Helbig R, Dantoft W, Gimber N, Visa N. Splice-site mutations cause Rrp6-mediated nuclear retention of the unspliced RNAs and transcriptional downregulation of the splicing-defective genes. PLoS One. 2010;5:11540. PubMed PMC

Fong YW, Zhou Q. Stimulatory effect of splicing factors on transcriptional elongation. Nature. 2001;414:929–933. PubMed

Alexander MR, Wheatley AK, Center RJ, Purcell DF. Efficient transcription through an intron requires the binding of an Sm-type U1 snRNP with intact stem loop II to the splice donor. Nucleic Acids Res. 2010;38:3041–3053. PubMed PMC

Sims RJ, 3rd, Millhouse S, Chen CF, Lewis BA, Erdjument-Bromage H, Tempst P, et al. Recognition of trimethylated histone H3 lysine 4 facilitates the recruitment of transcription postinitiation factors and pre-mRNA splicing. Mol Cell. 2007;28:665–676. PubMed PMC

Vermeulen M, Eberl HC, Matarese F, Marks H, Denissov S, Butter F, et al. Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers. Cell. 2010;142:967–980. PubMed

Luco RF, Pan Q, Tominaga K, Blencowe BJ, Pereira-Smith OM, Misteli T. Regulation of alternative splicing by histone modifications. Science. 2010;327:996–1000. PubMed PMC

Shilatifard A. Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation. Curr Opin Cell Biol. 2008;20:341–348. PubMed PMC

Dou Y, Milne TA, Ruthenburg AJ, Lee S, Lee JW, Verdine GL, et al. Regulation of MLL1 H3K4 methyltransferase activity by its core components. Nat Struct Mol Biol. 2006;13:713–719. PubMed

Steward MM, Lee JS, O'Donovan A, Wyatt M, Bernstein BE, Shilatifard A. Molecular regulation of H3K4 trimethylation by ASH2L, a shared subunit of MLL complexes. Nat Struct Mol Biol. 2006;13:852–854. PubMed

Bernstein BE, Kamal M, Lindblad-Toh K, Bekiranov S, Bailey DK, Huebert DJ, et al. Genomic maps and comparative analysis of histone modifications in human and mouse. Cell. 2005;120:169–181. PubMed

Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, et al. High-resolution profiling of histone methylations in the human genome. Cell. 2007;129:823–837. PubMed

Heintzman ND, Stuart RK, Hon G, Fu Y, Ching CW, Hawkins RD, et al. Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet. 2007;39:311–318. PubMed

Guenther MG, Levine SS, Boyer LA, Jaenisch R, Young RA. A chromatin landmark and transcription initiation at most promoters in human cells. Cell. 2007;130:77–88. PubMed PMC

Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, et al. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature. 2007;448:553–560. PubMed PMC

Schneider R, Bannister AJ, Myers FA, Thorne AW, Crane-Robinson C, Kouzarides T. Histone H3 lysine 4 methylation patterns in higher eukaryotic genes. Nat Cell Biol. 2004;6:73–77. PubMed

Baker SP, Grant PA. The SAGA continues: expanding the cellular role of a transcriptional co-activator complex. Oncogene. 2007;26:5329–5340. PubMed PMC

Hassan AH, Prochasson P, Neely KE, Galasinski SC, Chandy M, Carrozza MJ, et al. Function and selectivity of bromodomains in anchoring chromatin-modifying complexes to promoter nucleosomes. Cell. 2002;111:369–379. PubMed

Martinez E, Palhan VB, Tjernberg A, Lymar ES, Gamper AM, Kundu TK, et al. Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo. Mol Cell Biol. 2001;21:6782–6795. PubMed PMC

Zhang P, Du J, Sun B, Dong X, Xu G, Zhou J, et al. Structure of human MRG15 chromo domain and its binding to Lys36-methylated histone H3. Nucleic Acids Res. 2006;34:6621–6628. PubMed PMC

Cai Y, Jin J, Tomomori-Sato C, Sato S, Sorokina I, Parmely TJ, et al. Identification of new subunits of the multiprotein mammalian TRRAP/TIP60-containing histone acetyltransferase complex. J Biol Chem. 2003;278:42733–42736. PubMed

Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004;24:1884–1896. PubMed PMC

Pardo PS, Leung JK, Lucchesi JC, Pereira-Smith OM. MRG15, a novel chromodomain protein, is present in two distinct multiprotein complexes involved in transcriptional activation. J Biol Chem. 2002;277:50860–50866. PubMed

Yochum GS, Ayer DE. Role for the mortality factors MORF4, MRGX and MRG15 in transcriptional repression via associations with Pf1, mSin3A and Transducin-Like Enhancer of Split. Mol Cell Biol. 2002;22:7868–7876. PubMed PMC

Jelinic P, Pellegrino J, David G. A novel mammalian complex containing Sin3B mitigates histone acetylation and RNAPII progression within transcribed loci. Mol Cell Biol. 2011 PubMed PMC

Hayakawa T, Ohtani Y, Hayakawa N, Shinmyozu K, Saito M, Ishikawa F, et al. RBP2 is an MRG15 complex component and downregulates intragenic histone H3 lysine 4 methylation. Genes Cells. 2007;12:811–826. PubMed

Lee N, Erdjument-Bromage H, Tempst P, Jones RS, Zhang Y. The H3K4 demethylase lid associates with and inhibits histone deacetylase Rpd3. Mol Cell Biol. 2009;29:1401–1410. PubMed PMC

Govind CK, Qiu H, Ginsburg DS, Ruan C, Hofmeyer K, Hu C, et al. Phosphorylated Pol II CTD recruits multiple HDACs, including Rpd3C(S), for methylation-dependent deacetylation of ORF nucleosomes. Mol Cell. 2010;39:234–246. PubMed PMC

Joshi AA, Struhl K. Eaf3 chromodomain interaction with methylated H3-K36 links histone deacetylation to Pol II elongation. Mol Cell. 2005;20:971–978. PubMed

Carrozza MJ, Li B, Florens L, Suganuma T, Swanson SK, Lee KK, et al. Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. Cel. 2005;123:581–592. PubMed

Vakoc CR, Mandat SA, Olenchock BA, Blobel GA. Histone H3 lysine 9 methylation and HP1gamma are associated with transcription elongation through mammalian chromatin. Mol Cell. 2005;19:381–391. PubMed

Saint-André V, Batsché E, Rachez C, Muchardt C. Histone H3 lysine 9 trimethylation and HP1γ favor inclusion of alternative exons. Nat Struct Mol Biol. 2011;18:337–344. PubMed

Piacentini L, Fanti L, Negri R, Del Vescovo V, Fatica A, Altieri F, et al. Heterochromatin protein 1 (HP1a) positively regulates euchromatic gene expression through RNA transcript association and interaction with hnRNPs in Drosophila. PLoS Genet. 2009;5:1000670. PubMed PMC

Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell. 2010;142:409–419. PubMed PMC

Xue Y, Zhou Y, Wu T, Zhu T, Ji X, Kwon YS, et al. Genome-wide analysis of PTB-RNA interactions reveals a strategy used by the general splicing repressor to modulate exon inclusion or skipping. Mol Cell. 2009;36:996–1006. PubMed PMC

Ferguson M, Henry PA, Currie RA. Histone deacetylase inhibition is associated with transcriptional repression of the Hmga2 gene. Nucleic Acids Res. 2003;31:3123–3133. PubMed PMC

Rustighi A, Tessari MA, Vascotto F, Sgarra R, Giancotti V, Manfioletti G. A polypyrimidine/polypurine tract within the Hmga2 minimal promoter: a common feature of many growth-related genes. Biochemistry. 2002;41:1229–1240. PubMed

Tai HH, Geisterfer M, Bell JC, Moniwa M, Davie JR, Boucher L, et al. CHD1 associates with NCoR and histone deacetylase as well as with RNA splicing proteins. Biochem Biophys Res Commun. 2003;308:170–176. PubMed

Pryde F, Khalili S, Robertson K, Selfridge J, Ritchie AM, Melton DW, et al. 53BP1 exchanges slowly at the sites of DNA damage and appears to require RNA for its association with chromatin. J Cell Sci. 2005;118:2043–2055. PubMed

Young JI, Hong EP, Castle JC, Crespo-Barreto J, Bowman AB, Rose MF, et al. Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2. Proc Natl Acad Sci USA. 2005;102:17551–17558. PubMed PMC

TALE-directed local modulation of H3K9 methylation shapes exon recognition

CRE promoter sites modulate alternative splicing via p300-mediated histone acetylation

The C-terminal domain of Brd2 is important for chromatin interaction and regulation of transcription and alternative splicing