Ryo Nabeshima, Osamu Nishimura, Takako Maeda, Natsumi Shimizu, Takahiro Ide, Kenta Yashiro, Yasuo Sakai, Chikara Meno, Mitsutaka Kadota, Hidetaka Shiratori, Shigehiro Kuraku, Hiroshi Hamada (2018) Loss of Fam60a, a Sin3a subunit, results in embryonic lethality and is associated with aberrant methylation at a subset of gene promoters., eLife, Volume 7
Published in 2018 Aug 2 (Electronic publication in Aug. 2, 2018, midnight )
(Abstract) We have examined the role of Fam60a, a gene highly expressed in embryonic stem cells, in mouse development. Fam60a interacts with components of the Sin3a-Hdac transcriptional corepressor complex, and most Fam60a(-/-) 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 Fam60a(-/-) embryos. The DNA methylation level of the Fam60a target gene Adhfe1 is maintained at embryonic day (E) 7.5 but markedly reduced at E9.5 in Fam60a(-/-) 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 Fam60a(-/-) 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.(MeSH Terms)