OBOX regulates mouse zygotic genome activation and early development

Area of Science:

• Developmental Biology
• Genetics
• Molecular Biology

Background:

• Zygotic genome activation (ZGA) is essential for the maternal-to-zygotic transition in mammalian embryos.
• The specific transcription factors driving mammalian ZGA in vivo have remained largely unidentified.

Purpose of the Study:

• To identify key transcription factors regulating mammalian zygotic genome activation (ZGA) in vivo.
• To elucidate the molecular mechanisms by which OBOX proteins control ZGA and early embryogenesis.

Main Methods:

• Generation and analysis of Obox knockout mouse models (maternal and zygotic deficiencies).
• Chromatin-binding analysis to identify OBOX targets.
• RNA polymerase II relocation studies and chromatin accessibility assays.
• Ectopic expression of OBOX in mouse embryonic stem cells.

Main Results:

• OBOX transcription factors (OBOX1-OBOX8) are identified as critical regulators of mouse ZGA.
• Obox deficiency leads to a two-cell to four-cell developmental arrest with impaired ZGA, which can be rescued by restoring OBOX function.
• OBOX proteins facilitate RNA polymerase II preconfiguration to ZGA gene promoters and enhancers, impacting chromatin accessibility.
• Ectopic OBOX expression activates ZGA genes and MERVL repeats in mouse embryonic stem cells.

Conclusions:

• OBOX transcription factors are essential for mouse ZGA and early embryonic development.
• Maternal and zygotic OBOX expression redundantly support embryonic development.
• OBOX regulates ZGA by orchestrating RNA polymerase II recruitment and chromatin accessibility transitions.