PUBLICATION

Sinhcaf-dependent histone deacetylation is essential for primordial germ cell specification

Authors
Tao, B., Hu, H., Chen, J., Chen, L., Luo, D., Sun, Y., Ge, F., Zhu, Z., Trudeau, V.L., Hu, W.
ID
ZDB-PUB-220510-20
Date
2022
Source
EMBO reports   23(6): e54387 (Journal)
Registered Authors
Hu, Wei, Sun, Yonghua, Trudeau, V.L., Zhu, Zuoyan
Keywords
Sinhcaf, germ plasm, histone deacetylases, kinesin, primordial germ cells
Datasets
GEO:GSE159162, GEO:GSE198516
MeSH Terms
  • Animals
  • Female
  • Germ Cells/metabolism
  • Histones*/metabolism
  • Male
  • RNA, Messenger/genetics
  • Zebrafish*/genetics
  • Zygote
PubMed
35532311 Full text @ EMBO Rep.
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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping