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Kairong Cui1,5, Chongzhi Zang2,5, Tae-Young Roh1, Dustin E. Schones1, Richard W. Childs3, Weiqun Peng2, and Keji Zhao1,4

1 Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892
2 Department of Physics, The George Washington University, Washington, DC 20052
3 Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892
4 Corresponding author
5 These authors contributed equally to this work.

Summary

Histone modifications are implicated in the maintenance and differentiation of stem cells. In this report, we analyzed genome-wide changes of gene expression and multiple histone modifications during differentiation of multipotent human primary hematopoietic stem/progenitor cells (HSCs/HPCs) into erythrocyte precursor cells. Our data indicate that H3K4me1, H3K9me1 and H3K27me1 associate with critical enhancers of differentiation genes prior to their activation, while H3K9me3 and H3K27me3 correlate with repression of distinct subsets of genes. The majority of genes associated with both H3K4me3 and H3K27me3 (bivalent modifications) in HSCs/HPCs become silent and lose H3K4me3 after differentiation. The bivalent genes that lose H3K27me3 and become activated after differentiation are associated with increased levels of H2A.Z, H3K4me1, H3K9me1 and paused RNA polymerase II in HSCs/HPCs. These results suggest that the fate of bivalent genes during differentiation is already programmed by chromatin modifications at the HSC/HPC stage.

Data

Cell type Data set Tag coordinate bed file Summary bed file
CD133+ H2A.Z H2A.Z H2A.Z
CD133+ H3K4me1 H3K4me1 H3K4me1
CD133+ H3K4me3 H3K4me3 H3K4me3
CD133+ H3K9me1 H3K9me1 H3K9me1
CD133+ H3K9me3 H3K9me3 H3K9me3
CD133+ H3K27me1 H3K27me1 H3K27me1
CD133+ H3K27me3 H3K27me3 H3K27me3
CD133+ H3K36me3 H3K36me3 H3K36me3
CD133+ H4K20me1 H4K20me1 H4K20me1
CD133+ Pol II Pol II Pol II
CD133+ H3K4me1-repeat H3K4me1-repeat H3K4me1-repeat
CD133+ H3K27me1-repeat H3K27me1-repeat H3K27me1-repeat
CD36+ H2A.Z H2A.Z H2A.Z
CD36+ H3K4me1 H3K4me1 H3K4me1
CD36+ H3K4me3 H3K4me3 H3K4me3
CD36+ H3K9me1 H3K9me1 H3K9me1
CD36+ H3K9me3 H3K9me3 H3K9me3
CD36+ H3K27me1 H3K27me1 H3K27me1
CD36+ H3K27me3 H3K27me3 H3K27me3
CD36+ H3K36me3 H3K36me3 H3K36me3
CD36+ H4K20me1 H4K20me1 H4K20me1
CD36+ Pol II Pol II Pol II
CD36+ H3K4me1-repeat H3K4me1-repeat H3K4me1-repeat
CD36+ H3K27me1-repeat H3K27me1-repeat H3K27me1-repeat

Information on file formats

Tag coordinate bed files -- contain coordinates for all uniquely mapped reads for each experiment. Each line is in the format:

chromosome start coordinate end coordinate match type strand


Summary bed files -- Bed files displaying the number of uniquely mapped reads in 200 bp windows. All read start coordinates are adjusted by 75 bp in the direction of the strand they map to before summing is done.

UCSC custom tracks -- Automatic linking of summary bed files, or nucleosome score files to the UCSC Genome Browser to create custom tracks.

(Note: all coordinates are from the Human Mar. 2006 (hg18) assembly)

Data corresponding to this project have been deposited in the Gene Expression Ombinbus under the accession number: GSE12646