CFP1 Regulates Histone H3K4 Trimethylation and Developmental Potential in Mouse Oocytes

Abstract

Trimethylation of histone H3 at lysine-4 (H3K4me3) is associated with eukaryotic gene promoters and poises their transcriptional activation during development. To examine the in vivo function of H3K4me3 in the absence of DNA replication, we deleted CXXC finger protein 1 (CFP1), the DNA-binding subunit of the SETD1 histone H3K4 methyltransferase, in developing oocytes. We find that CFP1 is required for H3K4me3 accumulation and the deposition of histone variants onto chromatin during oocyte maturation. Decreased H3K4me3 in oocytes caused global downregulation of transcription activity. Oocytes lacking CFP1 failed to complete maturation and were unable to gain developmental competence after fertilization, due to defects in cytoplasmic lattice formation, meiotic division, and maternal-zygotic transition. Our study highlights the importance of H3K4me3 in continuous histone replacement for transcriptional regulation, chromatin remodeling, and normal developmental progression in a non-replicative system.

Desiccation and supra‐zero temperature storage of cat germinal vesicles lead to less structural damage and similar epigenetic alterations compared to cryopreservation

“…What influence does lower H3K4me3 have on the oocyte? In murine oocytes, decreased H3K4me3 level has been linked to misexpression of genes essential for meiotic resumption, leading to failure to maturation (Xu, Chen et al, ; C. Yu et al, ). Consistent with its role in promoting oocyte maturation, increased H3K4me3 was associated with improving meiotic and developmental competence of porcine oocytes (X. X. Yu et al, ).…”

“…What influence does lower H3K4me3 have on the oocyte? In murine oocytes, decreased H3K4me3 level has been linked to misexpression of genes essential for meiotic resumption, leading to failure to maturation (Xu, Chen et al, 2017;C. Yu et al, 2017).…”

“…These histone modifications are observed in the growing oocytes in the mouse (Kageyama et al, ), pig (Endo, Naito, Aoki, Kume, & Tojo, ; X. X. Yu et al, ), cow (Zhang, Wang et al, ), sheep (Russo et al, ), cat (Phillips, Wildt, & Comizzoli, ), and human (A. Zhang et al, ). Disruption of trimethylation of H3K4 in the developing murine oocytes led to failed maturation and impeded maternal‐zygote transition (C. Yu et al, ). In the domestic cat, increased H3K4me3 coincided with GV competence acquisition, suggesting a potential correlation (Phillips et al, ).…”

“…Zhang et al, 2012). Disruption of trimethylation of H3K4 in the developing murine oocytes led to failed maturation and impeded maternal-zygote transition (C. Yu et al, 2017). In the domestic cat, increased H3K4me3 coincided with GV competence acquisition, suggesting a potential correlation (Phillips et al, 2012).…”

LSD1 contributes to programmed oocyte death by regulating the transcription of autophagy adaptor SQSTM1/p62

“…Recently, the importance of epigenetic modification in regulating somatic cell reprogramming as well as early embryo development has been widely reported (Liu et al, ; Matoba & Zhang, ; Yu et al, ). However, only a handful of studies have indicated that epigenetic modification plays an important role in controlling oocyte PCD during PF pool establishment (Sun et al, , ).…”