SET domain-containing protein 5 is required for expression of primordial germ cell specification-associated genes in murine embryonic stem cells.
Primordial germ cell (PGC) specification is one of the most fundamental processes in developmental biology. Because PGCs are a common source of both gametes, generation of PGCs from embryonic stem cells (ESCs) is a useful model for analysing the germ line lineage. Although several studies focused on the role of epigenetic regulation on PGC differentiation from ESCs in vitro have been published, germ line commitment remains poorly understood. Here, we show that SET domain-containing protein (Setd5), which has a previously unknown function, is essential for regulating germ cell-associated genes in murine ESCs (mESCs). Even though Setd5 knockdown with 3 distinct shRNAs did not affect expression of pluripotency genes or levels of global histone methylation, all 3 shRNAs significantly diminished the expression of early and late-stage PGC-associated genes. Furthermore, our immunoprecipitation assay showed that Setd5 can interact with Tbl1xr1 and Ctr9, which are components of 2 different transcriptional regulatory complexes, namely, NcoR1 corepressor complex and Paf1 complex, respectively, in mESCs. Taken together, our data suggest that Setd5 is required for maintaining PGC-associated genes and Setd5-associated protein complexes containing Tbl1xr1 and Ctr9, which in turn are likely involved in regulating germ cell-related genes in mESCs.
['Yu|Seung Eun|SE|', 'Kim|Min Seong|MS|', 'Park|Su Hyung|SH|', 'Yoo|Byong Chul|BC|', 'Kim|Kyung Hee|KH|', 'Jang|Yeun Kyu|YK|http://orcid.org/0000-0002-1342-4190']
D000818:Animals D002454:Cell Differentiation D053595:Embryonic Stem Cells D044127:Epigenesis, Genetic D018507:Gene Expression Regulation, Developmental D055785:Gene Knockdown Techniques D005854:Germ Cells D008780:Methyltransferases D051379:Mice D046912:Multiprotein Complexes D009687:Nuclear Proteins D010750:Phosphoproteins D039904:Pluripotent Stem Cells D018160:Receptors, Cytoplasmic and Nuclear D012097:Repressor Proteins
primordial germ cell murine embryonic stem cells Setd5 knockdown SET domain-containing histone methyltransferase 5