Transcription factor 3 cooperates with CXXC finger protein 1 to regulate histone H3K4 trimethylation and developmental competence in mouse oocytes.

Oocyte-specific deletion of Tcf3 in mice causes female infertility, with impaired meiotic maturation and early embryonic arrest at the two-cell stage linked to disrupted H3K4me3 landscapes.

• Why it matters: Maternal epigenetic and transcriptional remodeling during oogenesis is needed for developmental competence, but how specific transcription factors shape histone marks and maternal-to-zygotic transition remains unclear.
• What they did: The study identified TCF3 as a maternal regulator, showing that it cooperates with CXXC1 to direct H3K4me3 deposition at target promoters via the SETD1 complex, including at Pabpn1l.
• The result: TCF3–CXXC1 promoter targeting depends on their DNA-binding activity, and loss of Tcf3 disrupts maternal mRNA clearance and H3K4me3 establishment in maturing oocytes, enabling proper maternal-to-zygotic transition.

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