title: Chromatin density and splicing destiny: on the cross-talk between chromatin structure and splicing.
abstract: How are short exonic sequences recognized within the vast intronic oceans in which they reside? Despite decades of research, this remains one of the most fundamental, yet enigmatic, questions in the field of pre-mRNA splicing research. For many years, studies aiming to shed light on this process were focused at the RNA level, characterizing the manner by which splicing factors and auxiliary proteins interact with splicing signals, thereby enabling, facilitating and regulating splicing. However, we increasingly understand that splicing is not an isolated process; rather it occurs co-transcriptionally and is presumably also regulated by transcription-related processes. In fact, studies by our group and others over the past year suggest that DNA structure in terms of nucleosome positioning and specific histone modifications, which have a well established role in transcription, may also have a role in splicing. In this review we discuss evidence for the coupling between transcription and splicing, focusing on recent findings suggesting a link between chromatin structure and splicing, and highlighting challenges this emerging field is facing.
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel.
authors.forename: Schraga
authors.initials: S
authors.lastname: Schwartz
authors.forename: Gil
authors.initials: G
authors.lastname: Ast
mesh_terms: D017398:Alternative Splicing; D002843:Chromatin / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D019175:DNA Methylation; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D005091:Exons; D006657:Histones / Q000378:metabolism; D006801:Humans; D007438:Introns; D008954:Models, Biological; D008957:Models, Genetic; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D012333:RNA, Messenger; D012313:RNA; D012321:DNA-Directed RNA Polymerases
references.citation: Trends Genet. 2007 Jan;23(1):5-7
references.pmid: 17070958
references.citation: Trends Genet. 2001 Feb;17(2):100-7
references.pmid: 11173120
references.citation: FEBS Lett. 2008 Jun 18;582(14):1971-6
references.pmid: 18435923
references.citation: Cell Cycle. 2009 Oct 15;8(20):3420-4
references.pmid: 19823040
references.citation: BMC Bioinformatics. 2009 Dec 22;10:442
references.pmid: 20028554
references.citation: Cell. 2007 Feb 23;128(4):693-705
references.pmid: 17320507
references.citation: J Cell Sci. 2002 Oct 15;115(Pt 20):3865-71
references.pmid: 12244124
references.citation: PLoS Biol. 2006 Jun;4(6):e147
references.pmid: 16640457
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):1766-71
references.pmid: 19179398
references.citation: RNA. 2009 Oct;15(10):1896-908
references.pmid: 19656867
references.citation: Nat Rev Genet. 2009 May;10(5):295-304
references.pmid: 19308066
references.citation: Nat Struct Mol Biol. 2009 Sep;16(9):996-1001
references.pmid: 19684599
references.citation: Genes Dev. 2008 Oct 15;22(20):2786-98
references.pmid: 18923077
references.citation: Mol Cell. 2006 Dec 28;24(6):917-29
references.pmid: 17189193
references.citation: PLoS Comput Biol. 2009 Mar;5(3):e1000300
references.pmid: 19266014
references.citation: Mol Cell Biol. 2000 Mar;20(6):1899-910
references.pmid: 10688638
references.citation: Gene. 2005 Jun 6;352:57-62
references.pmid: 15862762
references.citation: Mol Cell. 2009 Feb 27;33(4):450-61
references.pmid: 19250906
references.citation: Genes Dev. 2006 May 1;20(9):1100-9
references.pmid: 16651655
references.citation: Mol Cell. 2009 Oct 23;36(2):245-54
references.pmid: 19854133
references.citation: Biochem J. 2009 Jan 1;417(1):15-27
references.pmid: 19061484
references.citation: Cell. 1983 Mar;32(3):681-94
references.pmid: 6550524
references.citation: Nature. 2007 Aug 9;448(7154):714-7
references.pmid: 17687327
references.citation: Mol Cell Biol. 1994 Nov;14(11):7219-25
references.pmid: 7523861
references.citation: EMBO J. 2003 Aug 15;22(16):4274-82
references.pmid: 12912924
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 27;106(43):18357-61
references.pmid: 19826084
references.citation: Nature. 2009 Sep 10;461(7261):193-8
references.pmid: 19741699
references.citation: Mol Cell. 2009 Oct 23;36(2):178-91
references.pmid: 19854129
references.citation: Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11193-8
references.pmid: 11572975
references.citation: Nucleic Acids Res. 2010 May;38(9):2788-98
references.pmid: 20097656
references.citation: Trends Genet. 2008 Dec;24(12):583-7
references.pmid: 18951646
references.citation: Curr Biol. 2003 Jul 15;13(14):1192-200
references.pmid: 12867029
references.citation: Science. 2010 Feb 19;327(5968):996-1000
references.pmid: 20133523
references.citation: Annu Rev Biochem. 2003;72:291-336
references.pmid: 12626338
references.citation: Mol Cell Biol. 2004 Oct;24(20):8963-9
references.pmid: 15456870
references.citation: Nat Struct Mol Biol. 2008 Aug;15(8):819-26
references.pmid: 18641664
references.citation: J Biol Chem. 2005 Nov 18;280(46):38814-22
references.pmid: 16166085
references.citation: Nat Genet. 1995 Feb;9(2):184-90
references.pmid: 7719347
references.citation: Nat Genet. 2003 Jun;34(2):187-92
references.pmid: 12740577
references.citation: Nat Struct Mol Biol. 2009 Nov;16(11):1128-33
references.pmid: 19820712
references.citation: Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):6975-80
references.pmid: 8692929
references.citation: EMBO J. 2008 Jan 23;27(2):406-20
references.pmid: 18157086
references.citation: PLoS Genet. 2009 Oct;5(10):e1000682
references.pmid: 19834536
references.citation: Biochim Biophys Acta. 2002 Sep 13;1577(2):308-24
references.pmid: 12213660
references.citation: Science. 2002 Oct 11;298(5592):416-9
references.pmid: 12376702
references.citation: RNA. 1996 Jul;2(7):641-51
references.pmid: 8756407
references.citation: Nucleic Acids Res. 1998 Dec 15;26(24):5568-72
references.pmid: 9837984
references.citation: J Mol Biol. 2002 Feb 8;316(1):7-17
references.pmid: 11829499
references.citation: Cell. 2007 Feb 23;128(4):683-92
references.pmid: 17320506
references.citation: Nat Rev Genet. 2004 Oct;5(10):773-82
references.pmid: 15510168
references.citation: Nat Struct Mol Biol. 2006 Jan;13(1):22-9
references.pmid: 16341228
references.citation: J Mol Biol. 1997 Apr 18;267(5):1171-85
references.pmid: 9150405
references.citation: Genes Dev. 2005 May 15;19(10):1211-26
references.pmid: 15905409
references.citation: Nature. 2009 Nov 19;462(7271):315-22
references.pmid: 19829295
references.citation: J Biol Chem. 2005 Aug 12;280(32):28927-35
references.pmid: 15944154
references.citation: Nat Struct Mol Biol. 2009 Sep;16(9):990-5
references.pmid: 19684600
references.citation: Genome Res. 2009 Oct;19(10):1732-41
references.pmid: 19687145
references.citation: Nat Rev Mol Cell Biol. 2010 Apr;11(4):264-75
references.pmid: 20197778
references.citation: Cell. 2007 May 18;129(4):823-37
references.pmid: 17512414
references.citation: Nature. 2010 Jan 28;463(7280):457-63
references.pmid: 20110989
references.citation: Nat Struct Mol Biol. 2006 Jan;13(1):5-7
references.pmid: 16395314
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4325-30
references.pmid: 19251664
references.citation: Mol Cell. 2008 Feb 1;29(2):271-8
references.pmid: 18243121
references.citation: Genome Res. 2009 Sep;19(9):1593-605
references.pmid: 19581485
references.citation: Nature. 1997 Jan 23;385(6614):357-61
references.pmid: 9002523
references.citation: Cell. 2008 Mar 7;132(5):887-98
references.pmid: 18329373
references.citation: Nat Rev Genet. 2007 Oct;8(10):749-61
references.pmid: 17726481
references.citation: Nat Genet. 2009 Mar;41(3):376-81
references.pmid: 19182803
references.citation: Mol Cell Biol. 2006 Dec;26(24):9185-95
references.pmid: 17030614
references.citation: J Biol Chem. 1995 Feb 10;270(6):2411-4
references.pmid: 7852296
references.citation: Cell. 2007 Feb 23;128(4):669-81
references.pmid: 17320505
references.citation: Mol Cell. 2003 Aug;12(2):525-32
references.pmid: 14536091
references.citation: Nat Struct Mol Biol. 2006 Sep;13(9):815-22
references.pmid: 16921380
references.citation: Biochemistry. 1994 Mar 1;33(8):2210-6
references.pmid: 8117678
references.citation: Nat Genet. 2006 Oct;38(10):1210-5
references.pmid: 16964265
references.citation: Science. 2009 Jul 31;325(5940):626-8
references.pmid: 19644123
references.citation: PLoS Comput Biol. 2009 Nov;5(11):e1000566
references.pmid: 19918365
references.citation: Mol Cell. 2008 Dec 5;32(5):727-34
references.pmid: 19061647
references.citation: Mol Cell. 2006 Mar 17;21(6):849-59
references.pmid: 16543153
references.citation: Mol Cell. 2007 Jun 22;26(6):867-81
references.pmid: 17588520
references.citation: Nat Struct Mol Biol. 2009 Jul;16(7):717-24
references.pmid: 19543290
references.citation: Trends Biochem Sci. 2000 Aug;25(8):381-8
references.pmid: 10916158
references.citation: Genes Dev. 1988 Jun;2(6):754-65
references.pmid: 3138163
references.citation: Nature. 2009 Mar 19;458(7236):362-6
references.pmid: 19092803
references.citation: Cell. 2009 May 15;137(4):708-20
references.pmid: 19450518
references.citation: Nature. 1998 Aug 27;394(6696):842
references.pmid: 9732866
references.citation: Cell. 2002 Feb 22;108(4):501-12
references.pmid: 11909521
references.citation: Trends Genet. 2009 Aug;25(8):335-43
references.pmid: 19596482
references.citation: Curr Opin Genet Dev. 2008 Apr;18(2):145-51
references.pmid: 18372167
references.citation: Mol Cell. 2007 Nov 30;28(4):665-76
references.pmid: 18042460
references.citation: Proc Natl Acad Sci U S A. 1987 Oct;84(19):6644-8
references.pmid: 3477794
references.citation: Cell. 1999 Aug 6;98(3):285-94
references.pmid: 10458604
references.citation: Mol Cell Biol. 1990 Nov;10(11):6059-63
references.pmid: 1978245
references.citation: J Am Chem Soc. 2010 Feb 17;132(6):1782-3
references.pmid: 20095602
references.citation: RNA. 2004 Oct;10(10):1489-98
references.pmid: 15383674
references.citation: Nature. 2006 Aug 17;442(7104):772-8
references.pmid: 16862119
references.citation: Mol Cell Biol. 2001 Nov;21(22):7617-28
references.pmid: 11604498
references.citation: J Biol Chem. 2002 Nov 8;277(45):43110-4
references.pmid: 12221105
references.citation: Nat Struct Mol Biol. 2006 Nov;13(11):973-80
references.pmid: 17028590
references.citation: Science. 2009 Jan 16;323(5912):401-4
references.pmid: 19074313
references.citation: EMBO J. 2007 Dec 12;26(24):4974-84
references.pmid: 18007591