title: Differential H3K4 methylation identifies developmentally poised hematopoietic genes.
abstract: Throughout development, cell fate decisions are converted into epigenetic information that determines cellular identity. Covalent histone modifications are heritable epigenetic marks and are hypothesized to play a central role in this process. In this report, we assess the concordance of histone H3 lysine 4 dimethylation (H3K4me2) and trimethylation (H3K4me3) on a genome-wide scale in erythroid development by analyzing pluripotent, multipotent, and unipotent cell types. Although H3K4me2 and H3K4me3 are concordant at most genes, multipotential hematopoietic cells have a subset of genes that are differentially methylated (H3K4me2+/me3-). These genes are transcriptionally silent, highly enriched in lineage-specific hematopoietic genes, and uniquely susceptible to differentiation-induced H3K4 demethylation. Self-renewing embryonic stem cells, which restrict H3K4 methylation to genes that contain CpG islands (CGIs), lack H3K4me2+/me3- genes. These data reveal distinct epigenetic regulation of CGI and non-CGI genes during development and indicate an interactive relationship between DNA sequence and differential H3K4 methylation in lineage-specific differentiation.
authors.affiliation: Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Orford
authors.forename: Peter
authors.initials: P
authors.lastname: Kharchenko
authors.forename: Weil
authors.initials: W
authors.lastname: Lai
authors.forename: Maria Carlota
authors.initials: MC
authors.lastname: Dao
authors.forename: David J
authors.initials: DJ
authors.lastname: Worhunsky
authors.forename: Adam
authors.initials: A
authors.lastname: Ferro
authors.forename: Viktor
authors.initials: V
authors.lastname: Janzen
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Park
authors.forename: David T
authors.initials: DT
authors.lastname: Scadden
mesh_terms: D000818:Animals; D001665:Binding Sites; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D018899:CpG Islands / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D050437:Genes, Developmental; D016678:Genome; D006413:Hematopoietic System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D008957:Models, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D014157:Transcription Factors; D008239:Lysine