期刊
DEVELOPMENT
卷 143, 期 10, 页码 1788-1799出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.130203
关键词
Setdb1; Heterochromatin; Retrotransposon; Unfolded protein response; Mouse
资金
- Deutsche Forschungsgemeinschaft [SFB684, SFB1064]
- Boehringer Ingelheim
- European Research Council Advanced Grant from the European Community's Seventh Framework Program [291740-LymphoControl]
- Brazilian National Council for Scientific and Technological Development (CNPq-Brazil
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) [204724/2013-9]
The H3K9me3-specific histone methyltransferase Setdb1 impacts on transcriptional regulation by repressing both developmental genes and retrotransposons. How impaired retrotransposon silencing may lead to developmental phenotypes is currently unclear. Here, we show that loss of Setdb1 in pro-B cells completely abrogates B cell development. In pro-B cells, Setdb1 is dispensable for silencing of lineage-inappropriate developmental genes. Instead, we detect strong derepression of endogenous murine leukemia virus (MLV) copies. This activation coincides with an unusual change in chromatin structure, with only partial loss of H3K9me3 and unchanged DNA methylation, but strongly increased H3K4me3. Production of MLV proteins leads to activation of the unfolded protein response pathway and apoptosis. Thus, our data demonstrate that B cell development depends on the proper repression of retrotransposon sequences through Setdb1.
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