Chromatin Signatures in Multipotent Human Hematopoietic Stem Cells Indicate the Fate of Bivalent Genes during Differentiation

Kairong Cui; Chongzhi Zang; Tae Young Roh; Dustin E. Schones; Richard W. Childs; Weiqun Peng; Keji Zhao

doi:10.1016/j.stem.2008.11.011

Chromatin Signatures in Multipotent Human Hematopoietic Stem Cells Indicate the Fate of Bivalent Genes during Differentiation

Kairong Cui, Chongzhi Zang, Tae Young Roh, Dustin E. Schones, Richard W. Childs, Weiqun Peng, Keji Zhao

Department of Life Science

Research output: Contribution to journal › Article › peer-review

508 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	80-93
Number of pages	14
Journal	Cell Stem Cell
Volume	4
Issue number	1
DOIs	https://doi.org/10.1016/j.stem.2008.11.011
State	Published - 9 Jan 2009

Bibliographical note

Funding Information:
We thank Dr. Susan Wong for helpful discussions and Dr. Warren Leonard for critical reading of the manuscript. The gene expression analysis using the Affymetrix microarrays was performed by the Gene Expression Core Facility of the National Heart, Lung, and Blood Institute. This work was supported by the Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute.

Keywords

STEMCELL
SYSBIO

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10.1016/j.stem.2008.11.011

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title = "Chromatin Signatures in Multipotent Human Hematopoietic Stem Cells Indicate the Fate of Bivalent Genes during Differentiation",

abstract = "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.",

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AU - Schones, Dustin E.

AU - Childs, Richard W.

AU - Peng, Weiqun

AU - Zhao, Keji

N1 - Funding Information: We thank Dr. Susan Wong for helpful discussions and Dr. Warren Leonard for critical reading of the manuscript. The gene expression analysis using the Affymetrix microarrays was performed by the Gene Expression Core Facility of the National Heart, Lung, and Blood Institute. This work was supported by the Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute.

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N2 - 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.

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Chromatin Signatures in Multipotent Human Hematopoietic Stem Cells Indicate the Fate of Bivalent Genes during Differentiation

Abstract

Bibliographical note

Keywords

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