HIRA and dPCIF1 coordinately establish totipotent chromatin and control orderly ZGA in Drosophila embryos

Proc Natl Acad Sci U S A. 2024 Nov 19;121(47):e2410261121. doi: 10.1073/pnas.2410261121. Epub 2024 Nov 14.

Abstract

Early embryos undergo profound changes in their genomic architecture to establish the totipotent state, enabling pioneer factors to access chromatin and drive zygotic genome activation (ZGA). However, the mechanisms by which the totipotent state is established and properly interpreted by pioneer factors to allow orderly ZGA remain unknown. Here, we identify the H3.3-specific chaperone HIRA as a factor involving establishing totipotent-state chromatin in Drosophila early embryos. Through cophase separation with HIRA, the pioneer factor GAGA factor (GAF) efficiently binds to H3.3-marked nucleosomes to activate major-wave zygotic genes. Importantly, dPCIF1, a chromatin-associated protein, antagonized the GAF-HIRA interaction by competitively binding to HIRA, thereby restricting GAF on earlier chromatin and avoiding premature ZGA. Hence, the coordinated action of HIRA and dPCIF1 ensures sequential ZGA from the minor to major wave in early embryos. This study provides insights into understanding how a totipotent state is established and properly controlled during ZGA.

Keywords: Drosophila; early embryo; pioneer factor; zygotic genome activation.

MeSH terms

  • Animals
  • Cell Cycle Proteins* / genetics
  • Cell Cycle Proteins* / metabolism
  • Chromatin* / metabolism
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster* / embryology
  • Drosophila melanogaster* / genetics
  • Drosophila melanogaster* / metabolism
  • Embryo, Nonmammalian / metabolism
  • Gene Expression Regulation, Developmental
  • Histone Chaperones / genetics
  • Histone Chaperones / metabolism
  • Histones / genetics
  • Histones / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Zygote* / metabolism

Substances

  • Drosophila Proteins
  • Chromatin
  • Cell Cycle Proteins
  • Hira protein, Drosophila
  • Histone Chaperones
  • Transcription Factors
  • Histones