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PMID: 21847099 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

H3K4 tri-methylation provides an epigenetic signature of active enhancers.

The EMBO journal ·Vol. 30 ·No. 20 ·2011-08-16 ·Pages 4198-210

Pekowska A, Benoukraf T, Zacarias-Cabeza J, Belhocine M, Koch F, Holota H, Imbert J, Andrau JC, Ferrier P, Spicuglia S

Abstract

Combinations of post-translational histone modifications shape the chromatin landscape during cell development in eukaryotes. However, little is known about the modifications exactly delineating functionally engaged regulatory elements. For example, although histone H3 lysine 4 mono-methylation (H3K4me1) indicates the presence of transcriptional gene enhancers, it does not provide clearcut information about their actual position and stage-specific activity. Histone marks were, therefore, studied here at genomic loci differentially expressed in early stages of T-lymphocyte development. The concomitant presence of the three H3K4 methylation states (H3K4me1/2/3) was found to clearly reflect the activity of bona fide T-cell gene enhancers. Globally, gain or loss of H3K4me2/3 at distal genomic regions correlated with, respectively, the induction or the repression of associated genes during T-cell development. In the Tcrb gene enhancer, the H3K4me3-to-H3K4me1 ratio decreases with the enhancer's strength. Lastly, enhancer association of RNA-polymerase II (Pol II) correlated with the presence of H3K4me3 and Pol II accumulation resulted in local increase of H3K4me3. Our results suggest the existence of functional links between Pol II occupancy, H3K4me3 enrichment and enhancer activity.

MeSH Terms
Animals CD3 Complex/immunology Cell Line Enhancer Elements, Genetic Epigenesis, Genetic Genes, T-Cell Receptor beta Histones/metabolism Lymphocyte Activation/genetics Lysine/metabolism Male Mice Mice, Inbred C57BL RNA Polymerase II/metabolism T-Lymphocytes/metabolism Thymus Gland/growth & development,metabolism
Chemicals
CD3 Complex Cd3e protein, mouse Histones RNA Polymerase II Lysine
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Pekowska Aleksandra
Centre d'Immunologie de Marseille-Luminy, Parc Scientifique de Luminy, Case 906, Marseille, France.
Benoukraf Touati
Zacarias-Cabeza Joaquin
Belhocine Mohamed
Koch Frederic
Holota Hélène
Imbert Jean
Andrau Jean-Christophe
Ferrier Pierre
Spicuglia Salvatore
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
1460-2075
DOI
10.1038/emboj.2011.295
Published
2011-08-16
Epub
2011-00-16
Pages
4198-210
Language
English
Region
England
NLM ID
8208664
PMCID
PMC3199384
Subset
IM
External Links
PubMed source DOI: 10.1038/emboj.2011.295 PMC Full Text View journal details
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