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PMID: 15684400 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Chromatin architecture near a potential 3' end of the igh locus involves modular regulation of histone modifications during B-Cell development and in vivo occupancy at CTCF sites.

Molecular and cellular biology ·Vol. 25 ·No. 4 ·2005-02-00 ·Pages 1511-25

Garrett FE, Emelyanov AV, Sepulveda MA, Flanagan P, Volpi S, Li F, Loukinov D, Eckhardt LA, Lobanenkov VV, Birshtein BK

Abstract

The murine Igh locus has a 3' regulatory region (3' RR) containing four enhancers (hs3A, hs1,2, hs3B, and hs4) at DNase I-hypersensitive sites. The 3' RR exerts long-range effects on class switch recombination (CSR) to several isotypes through its control of germ line transcription. By measuring levels of acetylated histones H3 and H4 and of dimethylated H3 (K4) with chromatin immunoprecipitation assays, we found that early in B-cell development, chromatin encompassing the enhancers of the 3' RR began to attain stepwise modifications typical of an open conformation. The hs4 enhancer was associated with active chromatin initially in pro- and pre-B cells and then together with hs3A, hs1,2, and hs3B in B and plasma cells. Histone modifications were similar in resting splenic B cells and in splenic B cells induced by lipopolysaccharide to undergo CSR. From the pro-B-cell stage onward, the approximately 11-kb region immediately downstream of hs4 displayed H3 and H4 modifications indicative of open chromatin. This region contained newly identified DNase I-hypersensitive sites and several CTCF target sites, some of which were occupied in vivo in a developmentally regulated manner. The open chromatin environment of the extended 3' RR in mature B cells was flanked by regions associated with dimethylated K9 of histone H3. Together, these data suggest that 3' RR elements are located within a specific chromatin subdomain that contains CTCF binding sites and developmentally regulated modules.

MeSH Terms
3' Flanking Region/genetics Acetylation/drug effects Animals B-Lymphocytes/immunology,metabolism Bone Marrow/immunology,metabolism CCCTC-Binding Factor Chromatin/genetics,immunology,metabolism DNA Primers/genetics DNA-Binding Proteins/genetics,immunology,metabolism Deoxyribonuclease I/metabolism Enhancer Elements, Genetic/genetics Histones/genetics,immunology,metabolism Immunoglobulin Class Switching/drug effects,genetics,immunology Lipopolysaccharides/pharmacology Locus Control Region/genetics Mice Repressor Proteins/genetics,immunology,metabolism Spleen/immunology,metabolism Transcription, Genetic/genetics
Chemicals
CCCTC-Binding Factor Chromatin Ctcf protein, mouse DNA Primers DNA-Binding Proteins Histones Lipopolysaccharides Repressor Proteins Deoxyribonuclease I
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Garrett Francine E
Albert Einstein College of Medicine, Department of Cell Biology, Bronx, NY 10461, USA.
Emelyanov Alexander V
Sepulveda Manuel A
Flanagan Patrick
Volpi Sabrina
Li Fubin
Loukinov Dmitry
Eckhardt Laurel A
Lobanenkov Victor V
Birshtein Barbara K
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.25.4.1511-1525.2005
Published
2005-02-00
Pages
1511-25
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC548023
Subset
IM
Grants
NCI NIH HHS · T32 CA009173 · United States
NIAID NIH HHS · AI30653 · United States
NCI NIH HHS · T32 CA09173 · United States
NCI NIH HHS · 5 F31 CA76942 · United States
NIAID NIH HHS · AI13509 · United States
NIAID NIH HHS · R37 AI013509 · United States
NIAID NIH HHS · R01 AI030653 · United States
NCI NIH HHS · F31 CA076942 · United States
NIAID NIH HHS · R01 AI013509 · United States
NCI NIH HHS · P30CA13330 · United States
NCI NIH HHS · P30 CA013330 · United States
NIAID NIH HHS · R01 AI030653-16 · United States
External Links
PubMed source DOI: 10.1128/MCB.25.4.1511-1525.2005 PMC Full Text View journal details
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