H2A.Z reinforces maternal H3K4me3 formation and is essential for meiotic progression in mouse oocytes
Mammalian oocytes establish a unique landscape of histone modifications, some of which are inherited by early embryos. How histone variants shape the maternal histone landscape remains unknown. Here, we map histone H2A variants in mouse fully grown oocytes (FGOs) and find that H2A.Z forms broad domains across intergenic regions, along non-canonical H3K4me3 (ncH3K4me3). During oocyte growth, H2A.Z progressively transitions from an active promoter-rich, canonical distribution to a non-canonical broad distribution (ncH2A.Z). Depletion of H2A.Z in oocytes partially impairs ncH3K4me3 formation and causes severe defects in meiotic progression, which resemble Mll2-knockout oocytes. Conversely, depletion of ncH3K4me3 by Mll2 knockout also causes a reduction of ncH2A.Z in FGOs. Thus, our study suggests that ncH2A.Z and ncH3K4me3 reinforce each other to form functional oocytes. Overall design: CATCH-seq and CUT&RUN of canonical H2A and H2A variants, including H2A.Z and TH2A, in fully grown oocytes. CATCH-seq of H2A.Z in oocytes from 4 stages, including primary (5 days), secondary (10 days), preantral (15 days) stage of growing oocytes, and the fully grown stage of oocyte (28 days FGO) were conducted to profiling H2A.Z's landscape. Also, CATCH-seq of 10d growing oocytes with control and amanitin treated were performed. H2A.Z, H3K4me3, H3K27me3 and H2AK119ub1 CATCH-seq were performed in H2A.Z control and H2A.Z DKO FGO oocytes. H2A.Z and H3K4me3 CATCH-seq were performed in Mll2 wild type and Mll2 KO FGO oocytes.