Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells.
Higher eukaryotes must adapt a totipotent genome to specialized cell types with stable but limited functions. One potential mechanism for lineage restriction is changes in chromatin, and differentiation-related chromatin changes have been observed for individual genes. We have taken a genome-wide view of histone H3 lysine 9 dimethylation (H3K9Me2) and find that differentiated tissues show surprisingly large K9-modified regions (up to 4.9 Mb). These regions are highly conserved between human and mouse and are differentiation specific, covering only approximately 4% of the genome in undifferentiated mouse embryonic stem (ES) cells, compared to 31% in differentiated ES cells, approximately 46% in liver and approximately 10% in brain. These modifications require histone methyltransferase G9a and are inversely related to expression of genes within the regions. We term these regions large organized chromatin K9 modifications (LOCKs). LOCKs are substantially lost in cancer cell lines, and they may provide a cell type-heritable mechanism for phenotypic plasticity in development and disease.
Wen
Bo
B
Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Wu
Hao
H
Shinkai
Yoichi
Y
Irizarry
Rafael A
RA
Feinberg
Andrew P
AP
D000818:Animals; D001921:Brain / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D002874:Chromosome Mapping; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000502:physiology*; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D006367:HeLa Cells; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008239:Lysine / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009928:Organ Specificity; D011496:Protein Methyltransferases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology
D006657:Histones; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine