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Tissue-specific DNA demethylation is required for proper B-cell differentiation and function

Item Type:Article
Title:Tissue-specific DNA demethylation is required for proper B-cell differentiation and function
Creators Name:Orlanski, S. and Labi, V. and Reizel, Y. and Spiro, A. and Lichtenstein, M. and Levin-Klein, R. and Koralov, S.B. and Skversky, Y. and Rajewsky, K. and Cedar, H. and Bergman, Y.
Abstract:There is ample evidence that somatic cell differentiation during development is accompanied by extensive DNA demethylation of specific sites that vary between cell types. Although the mechanism of this process has not yet been elucidated, it is likely to involve the conversion of 5mC to 5hmC by Tet enzymes. We show that a Tet2/Tet3 conditional knockout at early stages of B-cell development largely prevents lineage-specific programmed demethylation events. This lack of demethylation affects the expression of nearby B-cell lineage genes by impairing enhancer activity, thus causing defects in B-cell differentiation and function. Thus, tissue-specific DNA demethylation appears to be necessary for proper somatic cell development in vivo.
Keywords:Tet2/Tet3, Chromatin, Differentially Methylated Regions, DMRs, Animals, Mice
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Volume:113
Number:18
Page Range:5018-5023
Date:3 May 2016
Official Publication:https://doi.org/10.1073/pnas.1604365113
PubMed:View item in PubMed

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