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Loss of Fam60a, a Sin3a subunit, results in embryonic lethality and is associated with aberrant methylation at a subset of gene promoters
Ist Teil von
eLife, 2018-08, Vol.7
Ort / Verlag
England: eLife Sciences Publications, Ltd
Erscheinungsjahr
2018
Quelle
MEDLINE
Beschreibungen/Notizen
We have examined the role of
, a gene highly expressed in embryonic stem cells, in mouse development. Fam60a interacts with components of the Sin3a-Hdac transcriptional corepressor complex, and most
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
embryos. The DNA methylation level of the Fam60a target gene
is maintained at embryonic day (E) 7.5 but markedly reduced at E9.5 in
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
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.