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Localized DNA Demethylation at Recombination Intermediates during Immunoglobulin Heavy Chain Gene Assembly
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نویسنده
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selimyan r. ,gerstein r.m. ,ivanova i. ,precht p. ,subrahmanyam r. ,perlot t. ,alt f.w. ,sen r.
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منبع
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plos biology - 2013 - دوره : 11 - شماره : 1
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چکیده
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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 (dh) and joining (jh) gene segments were methylated,djh 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,eμ. we propose that demethylation occurs after the first recombination step and may mark the junction for secondary recombination.
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آدرس
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laboratory of molecular biology and immunology,national institute on aging,national institutes of health,baltimore,md, United States, department of molecular genetics and microbiology,university of massachusetts medical school,worcester,ma, United States, laboratory of molecular biology and immunology,national institute on aging,national institutes of health,baltimore,md, United States, laboratory of molecular biology and immunology,national institute on aging,national institutes of health,baltimore,md, United States, laboratory of molecular biology and immunology,national institute on aging,national institutes of health,baltimore,md, United States, the howard hughes medical institute,the children's hospital,immune disease institute and department of genetics,harvard medical school,boston,ma,united states,institute of molecular biotechnology of the austrian academy of sciences,vienna, Austria, the howard hughes medical institute,the children's hospital,immune disease institute and department of genetics,harvard medical school,boston,ma, United States, laboratory of molecular biology and immunology,national institute on aging,national institutes of health,baltimore,md, United States
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Authors
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