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

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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	109367
Journal	iScience
Volume	27
Issue number	4
DOIs	https://doi.org/10.1016/j.isci.2024.109367
State	Published - 19 Apr 2024

Keywords

Biochemistry
Structural biology

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10.1016/j.isci.2024.109367

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title = "The winged helix domain of MORF binds CpG islands and the TAZ2 domain of p300",

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 (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.",

keywords = "Biochemistry, Structural biology",

author = "Becht, {Dustin C.} and Akinori Kanai and Soumi Biswas and Mohamed Halawa and Lei Zeng and Cox, {Khan L.} and Poirier, {Michael G.} and Zhou, {Ming Ming} and Xiaobing Shi and Akihiko Yokoyama and Kutateladze, {Tatiana G.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s)",

year = "2024",

month = apr,

day = "19",

doi = "10.1016/j.isci.2024.109367",

language = "English",

volume = "27",

journal = "iScience",

issn = "2589-0042",

publisher = "Elsevier Inc.",

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TY - JOUR

T1 - The winged helix domain of MORF binds CpG islands and the TAZ2 domain of p300

AU - Becht, Dustin C.

AU - Kanai, Akinori

AU - Biswas, Soumi

AU - Halawa, Mohamed

AU - Zeng, Lei

AU - Cox, Khan L.

AU - Poirier, Michael G.

AU - Zhou, Ming Ming

AU - Shi, Xiaobing

AU - Yokoyama, Akihiko

AU - Kutateladze, Tatiana G.

PY - 2024/4/19

Y1 - 2024/4/19

N2 - 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.

AB - 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.

KW - Biochemistry

KW - Structural biology

UR - http://www.scopus.com/inward/record.url?scp=85187570281&partnerID=8YFLogxK

U2 - 10.1016/j.isci.2024.109367

DO - 10.1016/j.isci.2024.109367

M3 - Article

AN - SCOPUS:85187570281

SN - 2589-0042

VL - 27

JO - iScience

JF - iScience

IS - 4

M1 - 109367

ER -

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

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Keywords

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