title: Nucleosomes are well positioned in exons and carry characteristic histone modifications.
abstract: The genomes of higher organisms are packaged in nucleosomes with functional histone modifications. Until now, genome-wide nucleosome and histone modification studies have focused on transcription start sites (TSSs) where nucleosomes in RNA polymerase II (RNAPII) occupied genes are well positioned and have histone modifications that are characteristic of expression status. Using public data, we here show that there is a higher nucleosome-positioning signal in internal human exons and that this positioning is independent of expression. We observed a similarly strong nucleosome-positioning signal in internal exons of Caenorhabditis elegans. Among the 38 histone modifications analyzed in man, H3K36me3, H3K79me1, H2BK5me1, H3K27me1, H3K27me2, and H3K27me3 had evidently higher signals in internal exons than in the following introns and were clearly related to exon expression. These observations are suggestive of roles in splicing. Thus, exons are not only characterized by their coding capacity, but also by their nucleosome organization, which seems evolutionarily conserved since it is present in both primates and nematodes.
authors.affiliation: The Linnaeus Centre for Bioinformatics, Uppsala University, Sweden.
authors.forename: Robin
authors.initials: R
authors.lastname: Andersson
authors.forename: Stefan
authors.initials: S
authors.lastname: Enroth
authors.forename: Alvaro
authors.initials: A
authors.lastname: Rada-Iglesias
authors.forename: Claes
authors.initials: C
authors.lastname: Wadelius
authors.forename: Jan
authors.initials: J
authors.lastname: Komorowski
mesh_terms: D017398:Alternative Splicing / Q000502:physiology; D000818:Animals; D002107:Caenorhabditis / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D005091:Exons / Q000235:genetics*; D005786:Gene Expression Regulation; D023061:Gene Order / Q000502:physiology; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009707:Nucleosomes / Q000378:metabolism* / Q000502:physiology*; D011323:Primates; D011499:Protein Processing, Post-Translational / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D006657:Histones; D009707:Nucleosomes; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase
references.citation: Science. 2007 Oct 19;318(5849):447-50
references.pmid: 17761849
references.citation: Curr Opin Cell Biol. 2005 Jun;17(3):294-301
references.pmid: 15901500
references.citation: PLoS Genet. 2008 Nov;4(11):e1000250
references.pmid: 18989456
references.citation: Nat Struct Mol Biol. 2006 Jan;13(1):22-9
references.pmid: 16341228
references.citation: Genes Dev. 2007 Jan 15;21(2):160-74
references.pmid: 17234882
references.citation: Nat Struct Mol Biol. 2006 Jan;13(1):5-7
references.pmid: 16395314
references.citation: Nucleic Acids Res. 1999 Aug 1;27(15):3219-28
references.pmid: 10454621
references.citation: Cell. 2008 Mar 7;132(5):887-98
references.pmid: 18329373
references.citation: Nucleic Acids Res. 2007 Jan;35(Database issue):D610-7
references.pmid: 17148474
references.citation: Cell. 2007 Feb 23;128(4):721-33
references.pmid: 17320509
references.citation: Science. 2008 Aug 1;321(5889):686-91
references.pmid: 18669861
references.citation: RNA. 2004 Oct;10(10):1489-98
references.pmid: 15383674
references.citation: Science. 2009 Jan 16;323(5912):401-4
references.pmid: 19074313
references.citation: Cell. 2007 Feb 23;128(4):707-19
references.pmid: 17320508
references.citation: J Cell Sci. 2002 Oct 15;115(Pt 20):3865-71
references.pmid: 12244124
references.citation: Genes Dev. 2008 Dec 15;22(24):3422-34
references.pmid: 19141475
references.citation: Cell. 2005 Nov 18;123(4):581-92
references.pmid: 16286007
references.citation: Gene. 2005 Jun 6;352:57-62
references.pmid: 15862762
references.citation: Nat Genet. 2008 Jul;40(7):897-903
references.pmid: 18552846
references.citation: Adv Exp Med Biol. 2007;623:175-89
references.pmid: 18380347
references.citation: Curr Opin Cell Biol. 2008 Jun;20(3):334-40
references.pmid: 18513937
references.citation: Mol Cell Biol. 2008 Feb;28(3):1041-6
references.pmid: 18039863
references.citation: Mol Cell Biol. 2004 Oct;24(20):9176-85
references.pmid: 15456888
references.citation: Mutagenesis. 2009 May;24(3):203-10
references.pmid: 19139058
references.citation: Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2380-3
references.pmid: 2006175
references.citation: Trends Genet. 2008 Dec;24(12):583-7
references.pmid: 18951646
references.citation: J Biol Chem. 2005 May 6;280(18):17732-6
references.pmid: 15760899
references.citation: Genome Res. 2008 Jul;18(7):1051-63
references.pmid: 18477713
references.citation: Curr Opin Cell Biol. 2008 Jun;20(3):260-5
references.pmid: 18436438
references.citation: J Mol Biol. 1996 Nov 8;263(4):503-10
references.pmid: 8918932
references.citation: EMBO J. 2008 Jan 23;27(2):406-20
references.pmid: 18157086
references.citation: Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6062-7
references.pmid: 15075390
references.citation: Nature. 2007 Aug 2;448(7153):553-60
references.pmid: 17603471
references.citation: Science. 2005 Jul 22;309(5734):626-30
references.pmid: 15961632
references.citation: J Biol Chem. 2008 Jan 18;283(3):1211-5
references.pmid: 18024426
references.citation: J Biol Chem. 2009 Jun 5;284(23):15701-7
references.pmid: 19332550
references.citation: Nat Nanotechnol. 2009 Apr;4(4):265-70
references.pmid: 19350039
references.citation: Cell. 2007 May 18;129(4):823-37
references.pmid: 17512414
references.citation: Nat Rev Genet. 2008 Mar;9(3):179-91
references.pmid: 18250624
references.citation: RNA. 2008 Feb;14(2):284-96
references.pmid: 18073345
references.citation: Nature. 2004 Nov 18;432(7015):406-11
references.pmid: 15525939
references.citation: J Biol Chem. 2000 Dec 22;275(51):39935-43
references.pmid: 10978320
references.citation: Nat Genet. 2009 Mar;41(3):376-81
references.pmid: 19182803
references.citation: J Biol Chem. 1995 Feb 10;270(6):2411-4
references.pmid: 7852296
references.citation: Mol Cell. 2003 Aug;12(2):525-32
references.pmid: 14536091
references.citation: Genes Dev. 1988 Jun;2(6):754-65
references.pmid: 3138163
references.citation: J Cell Sci. 2005 May 1;118(Pt 9):2043-55
references.pmid: 15840649
references.citation: Mutat Res. 2007 May 1;618(1-2):116-29
references.pmid: 17313961
references.citation: Curr Opin Genet Dev. 2008 Apr;18(2):145-51
references.pmid: 18372167
references.citation: Nat Rev Genet. 2009 Mar;10(3):161-72
references.pmid: 19204718