DRP004092
Fam60a is a component of the mSin3A-HDAC transcriptional corepressor complex and inhibits Tet-mediated DNA demethylation
Fam60a was identified as a highly expressed gene of unknown function in mouse embryonic stem cells. We have examined the role of Fam60a in mouse development. Most Fam60a mutant embryos manifest hypoplasia of visceral organs and die in utero. Fam60a interacts with components of the mSin3A-HDAC transcriptional corepressor complex and is recruited to the promoter regions of a subset of genes throughout the genome. Genome-wide gene expression analysis revealed that Fam60a target genes are either up- or down-regulated in Fam60a mutant embryos. In cultured cells, Fam60a inhibited the global conversion of 5-methylcytosine to 5-hydroxymethylcytosine mediated by TET1. Furthermore, bisulfite sequencing analysis of Fam60a target gene promoters showed that the DNA methylation level of Adhfe1 is maintained at embryonic day (E) 7.5 but is markedly reduced at E9.5 in Fam60a mutant embryos, suggesting that DNA demethylation is enhanced in the mutant. Our data suggest that Fam60a is a component of the mSin3A-HDAC complex and is required for proper embryogenesis, at least in part as a result of its inhibition of Tet-mediated DNA demethylation at specific gene promoters.