Epigenetic characterization of hematopoietic stem cell differentiation using miniChIP and bisulfite sequencing analysis

被引：106
作者：
Attema, Joanne L. [1 ]
Papathanasiou, Peter
Forsberg, E. Camilla
Xu, Jian
Smale, Stephen T.
Weissman, Irving L.
机构：
[1] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Dept Pathol, Stanford, CA 94305 USA
[2] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Dept Dev Biol, Stanford, CA 94305 USA
[3] Univ Calif Los Angeles, Howard Hughes Med Inst, Mol Biol Inst, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2007年 / 104卷 / 30期
关键词：
hematopoiesis; chromatin; gene expression; BETA-GLOBIN LOCUS; HISTONE H3; PRECEDES COMMITMENT; CHROMATIN-STRUCTURE; COMPLEX-FORMATION; PROGENITOR CELLS; GENE-EXPRESSION; IN-VITRO; LINEAGE; METHYLATION;
D O I：
10.1073/pnas.0704468104
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Hematopoietic stem cells (HSC) produce all blood cell lineages by virtue of their capacity to self-renew and differentiate into progenitors with decreasing cellular potential. Recent studies suggest that epigenetic mechanisms play an important role in controlling stem cell potency and cell fate decisions. To investigate this hypothesis in HSC, we have modified the conventional chromatin immunoprecipitation assay allowing for the analysis of 50,000 prospectively purified stem and progenitor cells. Together with bisulfite sequencing analysis, we found that methylated H3K4 and AcH3 and unmethylated CpG dinucleoticles colocalize across defined regulatory regions of lineage-affiliated genes in HSC. These active epigenetic histone modifications either accumulated or were replaced by increased DNA methylation and H3K27 trimethylation in committed progenitors consistent with gene expression. We also observed bivalent histone modifications at a lymphoidaffiliated gene in HSC and downstream transit-amplifying progenitors. Together, these data support a model in which epigenetic modifications serve as an important mechanism to control HSC multipotency.
引用
收藏
页码：12371 / 12376
页数：6
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