%0 Journal Article %J Dev Cell %D 2008 %T Differential H3K4 methylation identifies developmentally poised hematopoietic genes. %A Orford, Keith* %A Kharchenko, Peter* %A Lai, Weil %A Dao, Maria Carlota %A Worhunsky, David J %A Ferro, Adam %A Janzen, Viktor %A Park, Peter J** %A Scadden, David T** %K Animals %K Binding Sites %K Bone Marrow Cells %K Cell Differentiation %K Cell Line %K Cell Lineage %K CpG Islands %K Embryonic Stem Cells %K Gene Expression Regulation, Developmental %K Genes, Developmental %K Genome %K Hematopoietic System %K Histones %K Humans %K Lysine %K Methylation %K Mice %K Models, Genetic %K Promoter Regions, Genetic %K Transcription Factors %K Transcription Initiation Site %K Transcription, Genetic %X

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.

%B Dev Cell %V 14 %P 798-809 %8 2008 May %G eng %N 5 %1 http://www.ncbi.nlm.nih.gov/pubmed/18477461?dopt=Abstract %R 10.1016/j.devcel.2008.04.002