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

Elife. 2018 Aug 2;7:e36435. doi: 10.7554/eLife.36435.

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.

Keywords: DNA methylation; Sin3a; developmental biology; epigenetics; mouse; regenerative medicine; stem cell; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA Methylation / genetics*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • Embryonic Development / genetics*
  • Gene Expression Regulation, Developmental
  • Genome
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / genetics
  • Mice
  • Mice, Knockout
  • Promoter Regions, Genetic
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Sin3 Histone Deacetylase and Corepressor Complex

Substances

  • DNA-Binding Proteins
  • Fam60A protein, mouse
  • Repressor Proteins
  • SIN3A transcription factor
  • Histone Deacetylases
  • Sin3 Histone Deacetylase and Corepressor Complex