title: Sall4 is essential for mouse primordial germ cell specification by suppressing somatic cell program genes.
abstract: The Spalt-like 4 (Sall4) zinc finger protein is a critical transcription factor for pluripotency in embryonic stem cells (ESCs). It is also involved in the formation of a variety of organs, in mice, and humans. We report the essential roles of Sall4 in mouse primordial germ cell (PGC) specification. PGC specification is accompanied by the activation of the stem cell program and repression of the somatic cell program in progenitor cells. Conditional inactivation of Sall4 during PGC specification led to a reduction in the number of PGCs in embryonic gonads. Sall4(del/del) PGCs failed to translocate from the mesoderm to the endoderm and underwent apoptosis. In Sall4(del/del) PGC progenitors, somatic cell program genes (Hoxa1 and Hoxb1) were derepressed, while activation of the stem cell program was not impaired. We demonstrated that in differentiated ESCs, Sall4 bound to these somatic cell program gene loci, which are reportedly occupied by Prdm1 in embryonic carcinoma cells. Given that Sall4 and Prdm1 are known to associate with the histone deacetylase repressor complex, our findings suggest that Sall4 suppresses the somatic cell program possibly by recruiting the repressor complex in conjunction with Prdm1; therefore, it is essential for PGC specification.
authors.affiliation: Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
authors.forename: Yasuka L
authors.initials: YL
authors.lastname: Yamaguchi
authors.forename: Satomi S
authors.initials: SS
authors.lastname: Tanaka
authors.forename: Maho
authors.initials: M
authors.lastname: Kumagai
authors.forename: Yuka
authors.initials: Y
authors.lastname: Fujimoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Terabayashi
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Matsui
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Nishinakamura
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074462:Positive Regulatory Domain I-Binding Factor 1; D013234:Stem Cells; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C513258:Prdm1 protein, mouse; C509167:Sall4 protein, mouse; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1
keywords: HDAC; Ifitm1; Mouse; Primordial germ cells; Spalt-like 4