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

Ryo Nabeshima, Osamu Nishimura, Takako Maeda, Natsumi Shimizu, Takahiro Ide, Kenta Yashiro, Yasuo Sakai, Chikara Meno, Mitsutaka Kadota, Hidetaka Shiratori, Shigehiro Kuraku, Hiroshi Hamada

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article numbere36435
JournaleLife
Volume7
DOIs
Publication statusPublished - Aug 2 2018

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Methylation
DNA Methylation
Embryonic Structures
Genes
Co-Repressor Proteins
Genetic Promoter Regions
Embryonic Development
Genome
Stem cells
Gene Expression
DNA

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Loss of Fam60a, a Sin3a subunit, results in embryonic lethality and is associated with aberrant methylation at a subset of gene promoters. / Nabeshima, Ryo; Nishimura, Osamu; Maeda, Takako; Shimizu, Natsumi; Ide, Takahiro; Yashiro, Kenta; Sakai, Yasuo; Meno, Chikara; Kadota, Mitsutaka; Shiratori, Hidetaka; Kuraku, Shigehiro; Hamada, Hiroshi.

In: eLife, Vol. 7, e36435, 02.08.2018.

Research output: Contribution to journalArticle

Nabeshima, R, Nishimura, O, Maeda, T, Shimizu, N, Ide, T, Yashiro, K, Sakai, Y, Meno, C, Kadota, M, Shiratori, H, Kuraku, S & Hamada, H 2018, 'Loss of Fam60a, a Sin3a subunit, results in embryonic lethality and is associated with aberrant methylation at a subset of gene promoters', eLife, vol. 7, e36435. https://doi.org/10.7554/eLife.36435
Nabeshima, Ryo ; Nishimura, Osamu ; Maeda, Takako ; Shimizu, Natsumi ; Ide, Takahiro ; Yashiro, Kenta ; Sakai, Yasuo ; Meno, Chikara ; Kadota, Mitsutaka ; Shiratori, Hidetaka ; Kuraku, Shigehiro ; Hamada, Hiroshi. / Loss of Fam60a, a Sin3a subunit, results in embryonic lethality and is associated with aberrant methylation at a subset of gene promoters. In: eLife. 2018 ; Vol. 7.
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