Role of CxxC-finger Protein 1 in the Establishment of Epigenetic Landscapes in Mouse Oocytes

ABSTRACT: During oogenesis, oocytes gain competence to accomplish meiotic maturation and prepare for embryonic development following fertilization. Trimethylated histone H3 on lysine-4 (H3K4me3) mediates a wide range of nuclear events during these processes. Oocyte-specific knockout of CxxC-finger protein 1 (CXXC1, also known as CFP1), the chromatin-binding subunit of SETD1 methyltransferase, impairs the H3K4me3 accumulation during murine oogenesis and caused changes in chromatin configurations. This study investigated the changes of genomic H3K4me3 landscapes in oocytes after Cxxc1 knockout, as well as the influences of H3K4me3 changes on other epigenetic marks including DNA methylation, H3K27me3, H2AK119ub1, and H3K36me3. Chromatin immunoprecipitation and sequencing results indicated that H3K4me3 is globally decreased after abolishing Cxxc1, including both the promoter region and the gene body. The results also demonstrate that CXXC1 and another histone H3 methyltransferase MLL2 have nonoverlapping roles in mediating H3K4 trimethylation during oogenesis. In addition, Cxxc1 deletion caused a significant decrease of DNA methylation level in oocytes, and affected H3K27me3 and H2AK119ub1 distributions in the maternal genome, particularly at the regions that have high DNA methylation levels. The changes of epigenetic networks caused by Cxxc1 deletion correlated with transcription changes of the genes in the corresponding genomic regions. Taken together, this study provided mechanistic explanations underlying the phenotypes and molecular defects in Cxxc1 deleted oocytes, and highlighted a role of CXXC1 in orchestrating multiple factors to build up the appropriate epigenetic states of maternal genome during oocyte maturation.

ORGANISM(S): Mus musculus

PROVIDER: GSE159581 | GEO | 2021/02/04

REPOSITORIES: GEO