Figure 2.

Transcriptional regulation by KDM5. (A) Pre-initiation complex assembly is mediated by the selective anchoring of the basal transcription factor TFIID to the core promoter via TAF3 binding to H3K4me3. KDM5 proteins remove H3K4me3, thereby preventing transcription. (B) KDM5B functions as a scaffold protein and recruits the H3K9 methyltransferase, SETDB1, thereby suppressing retroelement expression by adding H3K9me3 [44]. (C) After pre-initiation complex formation, KDM5A supports the transcription of MYC target genes via the timely removal of H3K4me3, thereby allowing for the release of TFIID and for the phosphorylation of RNA polymerase II (RNAPII). KDM5A inhibition blocks H3K4me3 demethylation, thereby locking TFIID via TAF3 anchoring and impairing the activities of TFIIH and P-TEFb, which may be mediated by TAF7 [35]. (D) KDM5A promotes CLOCK–BMAL1-mediated transcription by inhibiting HDAC1 [52].