Discovery and Annotation of Functional Chromatin Signatures in the Human Genome 英文参考文献.docVIP

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Discovery and Annotation of Functional Chromatin Signatures in the Human Genome 英文参考文献.doc

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Discovery and Annotation of Functional Chromatin Signatures in the Human Genome 英文参考文献

DiscoveryandAnnotationofFunctionalChromatin SignaturesintheHumanGenome GaryHon1,2,WeiWang1,3*,BingRen1,2,4 * 1BioinformaticsProgram,UniversityofCaliforniaatSanDiego,LaJolla,California,UnitedStatesofAmerica,2LudwigInstituteforCancerResearch,UniversityofCalifornia atSanDiego,LaJolla,California,UnitedStatesofAmerica,3DepartmentofChemistryandBiochemistry,CenterforTheoreticalBiologicalPhysics,UniversityofCalifornia at San Diego, La Jolla, California, United States of America, 4Department of Cellular and Molecular Medicine and Moores Cancer Center, UCSD School of Medicine, UniversityofCaliforniaatSanDiego,LaJolla,California,UnitedStatesofAmerica Abstract Transcriptionalregulationinhumancellsisacomplexprocessinvolvingamultitudeofregulatoryelementsencodedbythe genome.Recentstudieshaveshownthatdistinctchromatinsignaturesmarkavarietyoffunctionalgenomicelementsand thatsubtlevariationsofthesesignaturesmarkelementswithdifferentfunctions.Toidentifynovelchromatinsignaturesin the human genome, we apply a de novo pattern-finding algorithm to genome-wide maps of histone modifications. We recover previously known chromatin signatures associated with promoters and enhancers. We also observe several chromatinsignatureswithstrongenrichmentofH3K36me3markingexons.CloserexaminationrevealsthatH3K36me3is foundonwell-positionednucleosomesatexon59ends,andthatthismodificationisaglobalmarkofexonexpressionthat alsocorrelateswithalternativesplicing.Additionally,weobservestrongenrichmentofH2BK5me1andH4K20me1athighly expressed exons near the 59 end, in contrast to the opposite distribution of H3K36me3-marked exons. Finally, we also recover frequently occurring chromatin signatures displaying enrichment of repressive histone modifications. These signatures mark distinct repeat sequences and are associated with distinct modes of gene repression. Together, these results highlight the rich information embedded in the human epigenome and underscore its value in studying gene regulation. Citation:HonG,Wa