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PMID: 21982154 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural

Two forms of loops generate the chromatin conformation of the immunoglobulin heavy-chain gene locus.

Cell ·Vol. 147 ·No. 2 ·2011-10-14 ·Pages 332-43

Guo C, Gerasimova T, Hao H, Ivanova I, Chakraborty T, Selimyan R, Oltz EM, Sen R

Abstract

The immunoglobulin heavy-chain (IgH) gene locus undergoes radial repositioning within the nucleus and locus contraction in preparation for gene recombination. We demonstrate that IgH locus conformation involves two levels of chromosomal compaction. At the first level, the locus folds into several multilooped domains. One such domain at the 3' end of the locus requires an enhancer, Eμ; two other domains at the 5' end are Eμ independent. At the second level, these domains are brought into spatial proximity by Eμ-dependent interactions with specific sites within the V(H) region. Eμ is also required for radial repositioning of IgH alleles, indicating its essential role in large-scale chromosomal movements in developing lymphocytes. Our observations provide a comprehensive view of the conformation of IgH alleles in pro-B cells and the mechanisms by which it is established.

MeSH Terms
Animals B-Lymphocytes/metabolism CCCTC-Binding Factor Cell Nucleus/genetics Chromatin/chemistry Enhancer Elements, Genetic Genes, Immunoglobulin Heavy Chain Immunoglobulin Heavy Chains/genetics Immunoglobulin Variable Region Mice Mice, 129 Strain Mice, Inbred C57BL Repressor Proteins/metabolism V(D)J Recombination YY1 Transcription Factor/metabolism
Chemicals
CCCTC-Binding Factor Chromatin Ctcf protein, mouse Immunoglobulin Heavy Chains Immunoglobulin Variable Region Repressor Proteins YY1 Transcription Factor Yy1 protein, mouse
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Guo Changying
Gene Regulation Section, Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD 21224, USA.
Gerasimova Tatiana
Hao Haiping
Ivanova Irina
Chakraborty Tirtha
Selimyan Roza
Oltz Eugene M
Sen Ranjan
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2011.08.049
Published
2011-10-14
Epub
2011-00-06
Pages
332-43
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC3685183
Subset
IM
Grants
Intramural NIH HHS · ZIA AG000373-05 · United States
NHLBI NIH HHS · P01 HL68744 · United States
NCI NIH HHS · R01 CA156690 · United States
NHLBI NIH HHS · P01 HL068744 · United States
NCI NIH HHS · R01 CA100905 · United States
NCI NIH HHS · CA100905 · United States
External Links
PubMed source DOI: 10.1016/j.cell.2011.08.049 PMC Full Text View journal details
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