Journal
PLOS BIOLOGY
Volume 11, Issue 1, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pbio.1001475
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Funding
- NIH [AI 2047, AI 43534]
- Intramural Research Program of the National Institute on Aging (Baltimore, MD)
- NIH NIDDK Diabetes Endocrinology Research Center [5 P30DK32520]
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Multiple epigenetic marks have been proposed to contribute to the regulation of antigen receptor gene assembly via V(D)J recombination. Here we provide a comprehensive view of DNA methylation at the immunoglobulin heavy chain (IgH) gene locus prior to and during V(D) J recombination. DNA methylation did not correlate with the histone modification state on unrearranged alleles, indicating that these epigenetic marks were regulated independently. Instead, pockets of tissue-specific demethylation were restricted to DNase I hypersensitive sites within this locus. Though unrearranged diversity (D-H) and joining (J(H)) gene segments were methylated, DJ(H) junctions created after the first recombination step were largely demethylated in pro-, pre-, and mature B cells. Junctional demethylation was highly localized, B-lineage-specific, and required an intact tissue-specific enhancer, E mu. We propose that demethylation occurs after the first recombination step and may mark the junction for secondary recombination.
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