Sinhcaf‐dependent histone deacetylation is essential for primordial germ cell specification. (9th May 2022)

• Record Type: Journal Article
• Authors: Tao, Binbin; Hu, Hongling; Chen, Ji; Chen, Lu; Luo, Daji; Sun, Yonghua; Ge, Feng; Zhu, Zuoyan; Trudeau, Vance L; Hu, Wei
• Is Part Of: EMBO reports. Volume 23:Number 6(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-05-09
• Subjects: germ plasm -- histone deacetylases -- kinesin -- primordial germ cells -- Sinhcaf; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.202154387
• Languages: English
• ISSNs: 1469-221X

Abstract

Abstract: Primordial germ cells (PGCs) are the progenitor cells that give rise to sperm and eggs. Sinhcaf is a recently identified subunit of the Sin3 histone deacetylase complex (SIN3A‐HDAC). Here, we provide evidence that Sinhcaf‐dependent histone deacetylation is essential for germ plasm aggregation and primordial germ cell specification. Specifically, maternal‐zygotic sinhcaf zebrafish mutants exhibit germ plasm aggregation defects, decreased PGC abundance and male‐biased sex ratio, which can be rescued by re‐expressing sinhcaf . Overexpression of sinhcaf results in excess PGCs and a female‐biased sex ratio. Sinhcaf binds to the promoter region of kif26ab . Loss of sinhcaf epigenetically switches off kif26ab expression by increasing histone 3 acetylation in the promoter region. Injection of kif26ab mRNA could partially rescue the germ plasm aggregation defects in sinhcaf mutant embryos. Taken together, we demonstrate a role of Sinhcaf in germ plasm aggregation and PGC specialization that is mediated by regulating the histone acetylation status of the kif26ab promoter to activate its transcription. Our findings provide novel insights into the function and regulatory mechanisms of Sinhcaf‐mediated histone deacetylation in PGC specification. SYNOPSIS: Sinhcaf, a subunit of the Sin3 histone deacetylase complex, modulates germ plasm aggregation and subsequent primordial germ cell specification. This represents a key mechanism controlling sexual differentiation in zebrafish. Sinhcaf‐mediated histone deacetylation is critical for zebrafish germ plasm aggregation and PGC specialization. The role of Sinhcaf in germ plasm aggregation and PGC specialization is mediated by the kinesin Kif26ab. Transcription of kif26ab is regulated by Sinhcaf by facilitating histone 3 deacetylation in its promoter region. Abstract : Sinhcaf, a subunit of the Sin3 histone deacetylase complex, modulates germ plasm aggregation and subsequent primordial germ cell specification. This represents a key mechanism controlling sexual differentiation in zebrafish.