Article The winged helix domain of MORF binds CpG islands and the TAZ2 domain of p300

Acetylation of histones by lysine acetyltransferases (KATs) provides a fundamental mechanism by which chromatin structure and transcriptional programs are regulated. Here, we describe a dual binding activity of the first winged helix domain of human MORF KAT (MORFWH1) that recognizes the TAZ2 domain ofp300 KAT (p300TAZ2) and CpG rich DNA sequences. Structural and biochemical studies identified distinct DNA and p300TAZ2binding sites, allowing MORFWH1to independently engage either ligand. Genomic data show that MORF/MOZWH1colocalizes with H3K18ac, a product of enzymatic activity of p300, onCpG rich promoters of target genes. Our findings suggest a functional cooperation of MORF and p300KATs in transcriptional regulation.