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Gene induction and repression during terminal erythropoiesis are mediated by distinct epigenetic changes

Wong, Piu, Hattangadi, Shilpa M., Cheng, Albert W., Frampton, Garrett M., Young, Richard A., Lodish, Harvey F.·2011·Blood
DOI 10.1182/blood-2011-03-341404
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Abstract

It is unclear how epigenetic changes regulate the induction of erythroid-specific genes during terminal erythropoiesis. Here we use global mRNA sequencing (mRNA-seq) and chromatin immunoprecipitation coupled to high-throughput sequencing (CHIP-seq) to investigate the changes that occur in mRNA levels, RNA polymerase II (Pol II) occupancy, and multiple posttranslational histone modifications when erythroid progenitors differentiate into late erythroblasts. Among genes induced during this developmental transition, there was an increase in the occupancy of Pol II, the activation marks H3K4me2, H3K4me3, H3K9Ac, and H4K16Ac, and the elongation methylation mark H3K79me2. In contrast, genes that were repressed during differentiation showed relative decreases in H3K79me2 levels yet had levels of Pol II binding and active histone marks similar to those in erythroid progenitors. We also found that relative changes in histone modification levels, in particular, H3K79me2 and H4K16ac, were most predictive of gene expression patterns. Our results suggest that in terminal erythropoiesis both promoter and elongation-associated marks contribute to the induction of erythroid genes, whereas gene repression is marked by changes in histone modifications mediating Pol II elongation. Our data map the epigenetic landscape of terminal erythropoiesis and suggest that control of transcription elongation regulates gene expression during terminal erythroid differentiation.

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Metadata

Authors
Wong, P., Hattangadi, S. M., Cheng, A. W., Frampton, G. M., Young, R. A., & Lodish, H. F.
Affiliations
  • Whitehead Institute for Biomedical Research, Cambridge, MA;
  • Departments of Biology and
Venue
Blood
Publisher
American Society of Hematology
Published
2011-10-20
Volume
118
Issue
16
Pages
e128-e138
ISSN
  • 0006-4971
  • 1528-0020
DOI
10.1182/blood-2011-03-341404
Cited by
120
References
2
Language
en

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