H3K4me3 Interactions with TAF3 Regulate Preinitiation Complex Assembly and Selective Gene Activation

Histone modifications regulate chromatin-dependent processes, yet the mechanisms by which they contribute to specific outcomes remain unclear. H3K4me3 is a prominent histone mark that is associated with active genes and promotes transcription through interactions with effector proteins that include initiation factor TFIID. We demonstrate that H3K4me3-TAF3 interactions direct global TFIID recruitment to active genes, some of which are p53 targets. Further analyses show that (1) H3K4me3 enhances p53-dependent transcription by stimulating preinitiation complex (PIC) formation; (2) H3K4me3, through TAF3 interactions, can act either independently or cooperatively with the TATA box to direct PIC formation and transcription; and (3) H3K4me3-TAF3/TFIID interactions regulate gene-selective functions of p53 in response to genotoxic stress. Our findings indicate a mechanism by which H3K4me3 directs PIC assembly for the rapid induction of specific p53 target genes. [Display omitted] ► H3K4me3 facilitates global TFIID recruitment to the core promoters of active genes ► By stimulating PIC formation, H3K4me3 enhances p53-dependent activation ► H3K4me3 acts both independently of and cooperatively with the TATA box ► Interactions between H3K4me3 and TAF3/TFIID regulate gene-selective functions of p53 H3K4me3 plays a causal role in transcription by recruiting the TAF3 subunit of TFIID to promoters and facilitating the assembly of the transcriptional preinitiation complex. This activity is required for the activation of rapidly induced genes, including some p53 targets.