ERP128216 PRJEB44193 ena-STUDY-Tianjin Medical University-08-04-2021-10:12:47:411-887 At peri-implantation, Kdm2bLF breaks down the barrier formed by H3K36me2 and nucleosome occupancy for PcG establishment at CGIs. Polycomb group (PcG) proteins are a family of chromatin regulators essential for post-implantation development. And PcG-mediated H3K27me3 is lost from promoters after fertilization while de novo established at peri-implantation. However, the molecular basis in unknown. Here we show that Kdm2b long isoform (Kdm2bLF) expression is specifically activated short after implantation and its H3K36me2 demethylase activity is required for the establishment of PcG functions at CpG islands (CGIs). Moreover, Kdm2bLF interacts with BRG1/BRM-associated factor (BAF). And Kdm2bLF-mediated H3K36me2 depletion at CGIs is vital for BAF enrichment and therefore gain of accessibility, which unexpectedly precedes PcG establishment. Consistently Kdm2bLF inactivation results in significantly delayed post-implantation development. Therefore, our study links Kdm2bLF's demethylase activity and partnership with BAF to the selective acquisition of PcG functions at CGIs at the time window of implantation. The Histone H3K36 demethylase KDM2B contributes to the establishment of Polycomb functions at CpG islands Polycomb group (PcG) proteins are a family of chromatin regulators essential for post-implantation development. And PcG-mediated H3K27me3 is lost from promoters after fertilization while de novo established at peri-implantation. However, the molecular basis in unknown. Here we show that Kdm2b long isoform (Kdm2bLF) expression is specifically activated short after implantation and its H3K36me2 demethylase activity is required for the establishment of PcG functions at CpG islands (CGIs). Moreover, Kdm2bLF interacts with BRG1/BRM-associated factor (BAF). And Kdm2bLF-mediated H3K36me2 depletion at CGIs is vital for BAF enrichment and therefore gain of accessibility, which unexpectedly precedes PcG establishment. Consistently Kdm2bLF inactivation results in significantly delayed post-implantation development. Therefore, our study links Kdm2bLF's demethylase activity and partnership with BAF to the selective acquisition of PcG functions at CGIs at the time window of implantation. ENA-FIRST-PUBLIC 2023-01-03 ENA-LAST-UPDATE 2023-01-03