H3.1/3.2 regulate the initial progression of the gene expression program.

Area of Science:

• Developmental Biology
• Epigenetics
• Genomics

Background:

• Zygotic genome transcription in mice begins at the one-cell stage and is initially promiscuous.
• Regulated gene expression, essential for early development, is established during the two-cell stage.

Purpose of the Study:

• To investigate the role of histone variants H3.1/3.2 in regulating gene expression changes during the mouse two-cell stage.

Main Methods:

• Immunocytochemistry to assess H3.1/3.2 nuclear deposition.
• Small interfering RNA (siRNA) to knockdown H3.1/3.2.
• Hi-C analysis to evaluate topologically associating domain formation.

Main Results:

• H3.1/3.2 nuclear deposition increased significantly from the one-cell to the late two-cell stage.
• H3.1/3.2 knockdown maintained open chromatin structure and promiscuous transcription in the late two-cell stage.
• Hi-C analysis revealed disrupted topologically associating domain formation in H3.1/3.2 knockdown embryos.

Conclusions:

• Histone variants H3.1/3.2 are essential for establishing closed chromatin structure during the two-cell stage.
• H3.1/3.2 facilitate the transition from promiscuous to regulated gene expression post-fertilization.
• These histone variants play a critical role in initiating the gene expression program for early embryonic development.