Narrow H3K4me2 is required for chicken PGC formation

J Cell Physiol. 2021 Feb;236(2):1391-1400. doi: 10.1002/jcp.29945. Epub 2020 Aug 4.

Abstract

The development of primordial germ cells (PGCs) undergoes epigenetic modifications. The study of histone methylation in regulating PGCs is beneficial to understand the development and differentiation mechanism of germ stem cells. Notably, it provides a theoretical basis for directed induction and mass acquisition in vitro. However, little is known about the regulation of PGC formation by histone methylation. Here, we found the high enrichment of H3K4me2 in the blastoderm, genital ridges, and testis. Chromatin immunoprecipitation sequencing was performed and the results revealed that genomic H3K4me2 is dynamic in embryonic stem cells, PGCs, and spermatogonial stem cells. This trend was consistent with the H3K4me2 enrichment in the gene promoter region. Additionally, narrow region triggered PGC-related genes (Bmp4, Wnt5a, and Tcf7l2) and signaling pathways (Wnt and transforming growth factor-β). After knocking down histone methylase Mll2 in vitro and vivo, the level of H3K4me2 decreased, inhibiting Cvh and Blimp1 expression, then repressing the formation of PGCs. Taken together, our study revealed the whole genome map of H3K4me2 in the formation of PGCs, contributing to improve the epigenetic study in PGC formation and providing materials for bird gene editing and rescue of endangered birds.

Keywords: Bmp4; H3K4me2; chicken; narrow; primordial germ cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Germline Stem Cells / cytology
  • Adult Germline Stem Cells / metabolism
  • Animals
  • Blastoderm / growth & development
  • Bone Morphogenetic Protein 4 / genetics*
  • Cell Differentiation / genetics
  • Chickens / genetics
  • Chickens / growth & development
  • Embryonic Stem Cells / metabolism
  • Epigenesis, Genetic / genetics*
  • Gene Expression Regulation, Developmental / genetics
  • Genitalia / growth & development
  • Germ Cells / growth & development
  • Histone Methyltransferases / genetics*
  • Male
  • Signal Transduction / genetics
  • Testis / growth & development*
  • Testis / metabolism
  • Transcription Factor 7-Like 2 Protein / genetics
  • Transforming Growth Factor beta / genetics
  • Wnt-5a Protein / genetics

Substances

  • Bone Morphogenetic Protein 4
  • Transcription Factor 7-Like 2 Protein
  • Transforming Growth Factor beta
  • Wnt-5a Protein
  • Histone Methyltransferases