Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan; Laboratory for Organismal Patterning, RIKEN Center for Developmental Biology, Kobe, Japan
Phyloinformatics Unit, RIKEN Center for Life Science Technologies, Kobe, Japan; Laboratory for Phyloinformatics, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
Takako Maeda
Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan
Laboratory for Organismal Patterning, RIKEN Center for Developmental Biology, Kobe, Japan
Kenta Yashiro
Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan
Yasuo Sakai
Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan
Chikara Meno
Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan
Mitsutaka Kadota
Phyloinformatics Unit, RIKEN Center for Life Science Technologies, Kobe, Japan; Laboratory for Phyloinformatics, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
Hidetaka Shiratori
Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan
Phyloinformatics Unit, RIKEN Center for Life Science Technologies, Kobe, Japan; Laboratory for Phyloinformatics, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan; Laboratory for Organismal Patterning, RIKEN Center for Developmental Biology, Kobe, Japan
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.
