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- W2120152757 abstract "Immunoglobulin genes V(D)J rearrangement during early lymphopoiesis is a critical process involving sequential recombination of the heavy and light chain loci. A number of transcription factors act together with temporally activated recombinases and chromatin accessibility changes to regulate this complex process. Here, we deleted the de novo DNA methyltransferases Dnmt3a and Dnmt3b in early B cells of conditionally targeted mice, and monitored the process of V(D)J recombination. Dnmt3a and Dnmt3b deletion resulted in precocious recombination of the immunoglobulin κ light chain without impairing the differentiation of mature B cells or overall B-cell development. Ex vivo culture of IL-7 restricted early B-cell progenitors lacking Dnmt3a and Dnmt3b showed precocious Vκ-Jκ rearrangements that are limited to the proximal Vκ genes. Furthermore, B-cell progenitors deficient in Dnmt3a and Dnmt3b showed elevated levels of germline transcripts at the proximal Vκ genes, alterations in methylation patterns at Igκ enhancer sites and increased expression of the transcription factor E2A. Our data suggest that Dnmt3a and Dnmt3b are critical to regulate the onset of Igκ light chain rearrangement during early B-cell development." @default.
- W2120152757 created "2016-06-24" @default.
- W2120152757 creator A5033312640 @default.
- W2120152757 creator A5055046712 @default.
- W2120152757 creator A5077535856 @default.
- W2120152757 creator A5089685016 @default.
- W2120152757 date "2015-06-16" @default.
- W2120152757 modified "2023-09-25" @default.
- W2120152757 title "De novo DNA Methyltransferases Dnmt3a and Dnmt3b regulate the onset of<i>Igκ</i>light chain rearrangement during early B-cell development" @default.
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- W2120152757 doi "https://doi.org/10.1002/eji.201445035" @default.
- W2120152757 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26059604" @default.
- W2120152757 hasPublicationYear "2015" @default.
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