Highlights d Poised enhancers are necessary for the induction of major anterior neural genes d Poised enhancers physically contact their target genes in embryonic stem cells d The interaction between poised enhancers and their target genes is PRC2 dependent d PRC2 provides major anterior neural loci with a permissive regulatory topology

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JMJD3 H3K27me3 demethylase plays an important role in the transcriptional response to different signaling pathways; however, the mechanism by which it facilitates transcription is unclear. Genome-wide analysis shows that JMJD3 regulates TGFβ response by promoting RNA polymerase II progression along the gene bodies.