Differential H3K4 methylation identifies developmentally poised hematopoietic genes.
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.
Orford
Keith
K
Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Kharchenko
Peter
P
Lai
Weil
W
Dao
Maria Carlota
MC
Worhunsky
David J
DJ
Ferro
Adam
A
Janzen
Viktor
V
Park
Peter J
PJ
Scadden
David T
DT
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
D006657:Histones; D014157:Transcription Factors; D008239:Lysine