Chromatin signatures in multipotent human hematopoietic stem cells indicate the fate of bivalent genes during differentiation.
Histone modifications have been implicated in stem cell maintenance and differentiation. We have analyzed genome-wide changes in gene expression and histone modifications during differentiation of multipotent human primary hematopoietic stem cells/progenitor cells (HSCs/HPCs) into erythrocyte precursors. Our data indicate that H3K4me1, H3K9me1, and H3K27me1 associate with enhancers of differentiation genes prior to their activation and correlate with basal expression, suggesting that these monomethylations are involved in the maintenance of activation potential required for differentiation. In addition, although the majority of genes associated with both H3K4me3 and H3K27me3 in HSCs/HPCs become silent and lose H3K4me3 after differentiation, those that lose H3K27me3 and become activated after differentiation are associated with increased levels of H2A.Z, H3K4me1, H3K9me1, H4K20me1, and RNA polymerase II in HSCs/HPCs. Thus, our data suggest that gene expression changes during differentiation are programmed by chromatin modifications present at the HSC/HPC stage and provide a resource for enhancer and promoter identification.
Cui
Kairong
K
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Zang
Chongzhi
C
Roh
Tae-Young
TY
Schones
Dustin E
DE
Childs
Richard W
RW
Peng
Weiqun
W
Zhao
Keji
K
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D018955:CD36 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage; D002462:Cell Membrane / Q000378:metabolism; D002843:Chromatin / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D015894:Genome, Human / Q000235:genetics; D006023:Glycoproteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D000071916:AC133 Antigen; D015703:Antigens, CD; D015415:Biomarkers; D018955:CD36 Antigens; D002843:Chromatin; D006023:Glycoproteins; D006657:Histones; D010455:Peptides; D014157:Transcription Factors