2019 journal article
Catalytically inactive Dnmt3b rescues mouse embryonic development by accessory and repressive functions
NATURE COMMUNICATIONS, 10.
MeSH headings : Animals; Biocatalysis; DNA (Cytosine-5-)-Methyltransferases / genetics; DNA (Cytosine-5-)-Methyltransferases / metabolism; DNA Methylation; Embryonic Development / genetics; Female; Gene Expression Regulation, Developmental; HEK293 Cells; Hedgehog Proteins / genetics; Humans; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Signal Transduction / genetics; Wnt Proteins / genetics
TL;DR:
It is shown that catalytically inactive Dnmt3b rescues a majority of methylation and expression changes in the absence of DnMT3b during mouse embryonic development and is linked to a control of major developmental pathways, including Wnt and hedgehog signaling.
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open access via www.nature.com (publisher PDF)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Source: Web Of Science
Added: October 21, 2019
AbstractDNA methylation regulates gene expression in a variety of processes, including mouse embryonic development. Four catalytically active enzymes function in mice as DNA methyltransferases (Dnmts) and as transcriptional regulators. Inactivation of Dnmt3b results in mouse embryonic lethality, but which activities are involved is unclear. Here we show that catalytically inactive Dnmt3b restores a majority of methylation and expression changes deregulated in the absence of Dnmt3b, and as a result, mice survive embryonic development. Thus, Dnmt3b functions as an accessory cofactor supporting catalytic activities performed by other Dnmts. We further demonstrate that Dnmt3b is linked to a control of major developmental pathways, including Wnt and hedgehog signaling. Dnmt3b directly represses Wnt9b whose aberrant up-regulation contributes to embryonic lethality of Dnmt3b knockout embryos. Our results highlight that Dnmt3b is a multifaceted protein that serves as an enzyme, an accessory factor for other methyltransferases, and as a transcriptional repressor in mouse embryogenesis.