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Loss of Fam60a, a Sin3a subunit, results in embryonic lethality and is associated with aberrant methylation at a subset of gene promoters

We have examined the role of , a gene highly expressed in embryonic stem cells, in mouse development. Fam60a interacts with components of the Sin3a-Hdac transcriptional corepressor complex, and most embryos manifest hypoplasia of visceral organs and die in utero. Fam60a is recruited to the promoter...

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Published in:eLife 2018-08, Vol.7
Main Authors: Nabeshima, Ryo, Nishimura, Osamu, Maeda, Takako, Shimizu, Natsumi, Ide, Takahiro, Yashiro, Kenta, Sakai, Yasuo, Meno, Chikara, Kadota, Mitsutaka, Shiratori, Hidetaka, Kuraku, Shigehiro, Hamada, Hiroshi
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Language:English
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Summary:We have examined the role of , a gene highly expressed in embryonic stem cells, in mouse development. Fam60a interacts with components of the Sin3a-Hdac transcriptional corepressor complex, and most embryos manifest hypoplasia of visceral organs and die in utero. Fam60a is recruited to the promoter regions of a subset of genes, with the expression of these genes being either up- or down-regulated in embryos. The DNA methylation level of the Fam60a target gene is maintained at embryonic day (E) 7.5 but markedly reduced at E9.5 in embryos, suggesting that DNA demethylation is enhanced in the mutant. Examination of genome-wide DNA methylation identified several differentially methylated regions, which were preferentially hypomethylated, in embryos. Our data suggest that Fam60a is required for proper embryogenesis, at least in part as a result of its regulation of DNA methylation at specific gene promoters.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.36435