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PMID: 12379744 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Hematopoietic-specific activators establish an overlapping pattern of histone acetylation and methylation within a mammalian chromatin domain.

Kiekhaefer CM, Grass JA, Johnson KD, Boyer ME, Bresnick EH

Abstract

Posttranslational modification of histones through acetylation, methylation, and phosphorylation is a common mode of regulating chromatin structure and, therefore, diverse nuclear processes. One such modification, methylated histone H3 at lysine-4 (H3-meK4), colocalizes with hyperacetylated histones H3 and H4 in mammalian chromatin. Whereas activators directly recruit acetyltransferases, the process whereby H3-meK4 is established is unknown. We tested whether the hematopoietic-specific activators NF-E2 and GATA-1, which mediate transactivation of the beta-globin genes, induce both histone acetylation and H3-meK4. Through the use of NF-E2- and GATA-1-null cell lines, we show that both activators induce H3 acetylation at the promoter upon transcriptional activation. However, analysis of H3-mek4 revealed that NF-E2 and GATA-1 differentially regulate chromatin modifications at the betamajor promoter. NF-E2, but not GATA-1, induces H3-meK4 at the promoter. Thus, under conditions in which NF-E2 and GATA-1 activate the transcription of an endogenous gene at least 570-fold, these activators differ in their capacity to induce H3-meK4. Despite strong H3-meK4 at hypersensitive site 2 of the upstream locus control region, neither factor was required to establish H3-meK4 at this site. These results support a model in which multiple tissue-specific activators collectively function to assemble a composite histone modification pattern, consisting of overlapping histone acetylation and methylation. As GATA-1 induced H3 acetylation, but not H3-meK4, at the promoter, H3 acetylation and H3-meK4 components of a composite histone modification pattern can be established independently.

MeSH Terms
Acetylation Animals Binding Sites Chromatin/metabolism DNA-Binding Proteins/genetics,metabolism Erythroid-Specific DNA-Binding Factors GATA1 Transcription Factor Hematopoiesis Histones/metabolism Mammals Methylation Mice NF-E2 Transcription Factor NF-E2 Transcription Factor, p45 Subunit Promoter Regions, Genetic Protein Processing, Post-Translational Protein Structure, Tertiary Trans-Activators/genetics,metabolism Transcription Factors/genetics,metabolism Tumor Cells, Cultured
Chemicals
Chromatin DNA-Binding Proteins Erythroid-Specific DNA-Binding Factors GATA1 Transcription Factor Gata1 protein, mouse Histones NF-E2 Transcription Factor NF-E2 Transcription Factor, p45 Subunit Nfe2 protein, mouse Trans-Activators Transcription Factors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kiekhaefer Carol M
Molecular and Cellular Pharmacology Program, Department of Pharmacology, University of Wisconsin Medical School, 1300 University Avenue, 383 Medical Sciences Center, Madison, WI 53706, USA.
Grass Jeffrey A
Johnson Kirby D
Boyer Meghan E
Bresnick Emery H
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
2002-10-29
Epub
2002-00-11
Pages
14309-14
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC137880
Subset
IM
Grants
NIDDK NIH HHS · DK55700 · United States
NIDDK NIH HHS · R01 DK050107 · United States
NIDDK NIH HHS · R01 DK055700 · United States
NIDDK NIH HHS · DK50107 · United States
NIDDK NIH HHS · R37 DK050107 · United States
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