GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE285nnn/GSE285236/suppl/GSE285236_mCherry_CpG.bwftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE285nnn/GSE285236/suppl/GSE285236_Rnaseh1_CpG.bwftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE285nnn/GSE285236/primaryOK200GenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE285236GEOGSEfalseR-loop maintains the deposition of H3K36me3 to prevent invasion of H3K4me3 during SN-oocyte development [EM-Seq]Establishment of epigenetic modifications in an orderly manner is crucial for oocyte maturation and embryonic development. R-loop (DNA/RNA hybrids) plays an important role in regulating genome stability, epigenetic modifications and gene expression. However, the specific functions and regulatory mechanisms of R-loop on the crosstalk between histone modifications during oocyte development remain unclear. Here, we find that loss of R-loop by overexpressing Rnaseh1 significantly slow down oocyte development. R-loop loss in germinal vesicle (GV) oocyte leads to downregulation of H3K36me3 at key oocyte developmental gene bodies, aberrant invasion of H3K4me3 into H3K36me3-marked regions, resulting in dysregulated gene expression and ultimately hindering oocyte development. Importantly, this dysregulated gene expression can be rescued by histone H3K36me3 methyltransferase SETD2 targeting on specific R-loop-dependent H3K36me3-marked regions. Together, this finding reveals that R-loop acts as a crucial regulator in controlling epigenetic crosstalk of H3K36me3 and H3K4me3 in maternal genome, ensuring normal oocyte development.2026/07/13GSE285236GSM8698946GSM8698948GSM8698947GSM869894928330285236Mus musculus