The winged helix domain of MORF binds CpG islands and the TAZ2 domain of p300
Dustin C. Becht,
Akinori Kanai,
Soumi Biswas,
Mohamed Halawa,
Lei Zeng,
Khan L. Cox,
Michael G. Poirier,
Ming-Ming Zhou,
Xiaobing Shi,
Akihiko Yokoyama,
Tatiana G. Kutateladze
Affiliations
Dustin C. Becht
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA
Akinori Kanai
Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, the University of Tokyo, Kashiwa, Chiba 277-0882, Japan
Soumi Biswas
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA
Mohamed Halawa
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA
Lei Zeng
Bethune Institute of Epigenetic Medicine, First Hospital of Jilin University, Changchun 130061, China; International Center of Future Science, Jilin University, Changchun 130012, China
Khan L. Cox
Department of Physics, Ohio State University, Columbus, OH 43210, USA
Michael G. Poirier
Department of Physics, Ohio State University, Columbus, OH 43210, USA
Ming-Ming Zhou
Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Xiaobing Shi
Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA
Akihiko Yokoyama
Tsuruoka Metabolomics Laboratory, National Cancer Center, Tsuruoka, Yamagata 997-0052, Japan
Tatiana G. Kutateladze
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA; Corresponding author
Summary: 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 of p300 KAT (p300TAZ2) and CpG rich DNA sequences. Structural and biochemical studies identified distinct DNA and p300TAZ2 binding sites, allowing MORFWH1 to independently engage either ligand. Genomic data show that MORF/MOZWH1 colocalizes with H3K18ac, a product of enzymatic activity of p300, on CpG rich promoters of target genes. Our findings suggest a functional cooperation of MORF and p300 KATs in transcriptional regulation.
