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

doi:10.1016/j.isci.2024.109367

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

iScience. 2024 Feb 29;27(4):109367. doi: 10.1016/j.isci.2024.109367. eCollection 2024 Apr 19.

Authors

Affiliations

¹ Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
² Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, the University of Tokyo, Kashiwa, Chiba 277-0882, Japan.
³ Bethune Institute of Epigenetic Medicine, First Hospital of Jilin University, Changchun 130061, China.
⁴ International Center of Future Science, Jilin University, Changchun 130012, China.
⁵ Department of Physics, Ohio State University, Columbus, OH 43210, USA.
⁶ Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁷ Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA.
⁸ Tsuruoka Metabolomics Laboratory, National Cancer Center, Tsuruoka, Yamagata 997-0052, Japan.

Abstract

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 (MORF_WH1) that recognizes the TAZ2 domain of p300 KAT (p300_TAZ2) and CpG rich DNA sequences. Structural and biochemical studies identified distinct DNA and p300_TAZ2 binding sites, allowing MORF_WH1 to independently engage either ligand. Genomic data show that MORF/MOZ_WH1 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.

Keywords: Biochemistry; Structural biology.