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PMID: 21860024 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Blood ·Vol. 118 ·No. 16 ·2011-10-20 ·Pages e128-38

Wong P, Hattangadi SM, Cheng AW, Frampton GM, Young RA, Lodish HF

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.

MeSH Terms
Acetylation Animals Cells, Cultured Chromatin/genetics,metabolism Chromatin Immunoprecipitation Epigenesis, Genetic Erythroblasts/cytology,metabolism Erythroid Precursor Cells/cytology,metabolism Erythropoiesis Gene Expression Regulation, Developmental High-Throughput Nucleotide Sequencing Histones/genetics,metabolism Humans Mice Mice, Inbred C57BL RNA Polymerase II/genetics,metabolism RNA, Messenger/genetics Sequence Analysis, RNA Transcriptional Activation
Chemicals
Chromatin Histones RNA, Messenger RNA Polymerase II
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wong Piu
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Hattangadi Shilpa M
Cheng Albert W
Frampton Garrett M
Young Richard A
Lodish Harvey F
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
1528-0020
DOI
10.1182/blood-2011-03-341404
Published
2011-10-20
Epub
2011-00-22
Pages
e128-38
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC3204918
Subset
IM
Grants
NIDDK NIH HHS · P30 DK072437 · United States
NIDDK NIH HHS · R01 DK071116 · United States
NHLBI NIH HHS · P01 HL032262 · United States
NHLBI NIH HHS · L40 HL086107 · United States
NIDDK NIH HHS · K08 DK076848 · United States
External Links
PubMed source DOI: 10.1182/blood-2011-03-341404 PMC Full Text View journal details
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