RNAPII progression through H3K27me3 enriched gene bodies require JMJD3 HDM activity. Mus musculus

Several signaling pathways require JMJD3 binding to promoters to activate the expression of target genes. Despite the known H3K27me3 demethylase activity of JMJD3 the transcriptional coactivator mechanism remains unclear. Here we reveal that JMJD3 promotes transcription of TGFb responsive genes through regulation of RNAPII progression on gene bodies. ChIPseq experiments demonstrate that upon TGFb treatment, JMJD3 and RNAPII.ser2P colocalyze extensively along intragenic regions of TGF target genes. According to these data, genome wide analysis shows that JMJD3 dependent TGF target genes are enriched in H3K27me3 prior to TGF signaling pathway activation. Further molecular analysis indicate that JMJD3 removes H3K27me3 and pave the way for the RNAPII.Overall, these findings uncover the mechanism of JMJD3 function in transcriptional activation Overall design: We performed chromatin immunoprecipitation followed by sequencing (ChIPseq) of H3K27me3 mark in mouse neural stem cells growing under standard conditions. We also performed ChIPseq of elongating RNAPII (Ser2P) and JMJD3 in neural stem cells stimulated with TGFb cytokine.