PHD finger protein 1 (PHF1) is a novel reader for histone H4R3 symmetric dimethylation and coordinates with PRMT5-WDR77/CRL4B complex to promote tumorigenesis

Nucleic Acids Research
Ruiqiong LiuYan Wang

Abstract

Histone post-translational modifications regulate chromatin structure and function largely through interactions with effector proteins that often contain multiple histone-binding domains. PHF1 [plant homeodomain (PHD) finger protein 1], which contains two kinds of histone reader modules, a Tudor domain and two PHD fingers, is an essential factor for epigenetic regulation and genome maintenance. While significant progress has been made in characterizing the function of the Tudor domain, the roles of the two PHD fingers are poorly defined. Here, we demonstrated that the N-terminal PHD finger of PHF1 recognizes symmetric dimethylation of H4R3 (H4R3me2s) catalyzed by PRMT5-WDR77. However, the C-terminal PHD finger of PHF1, instead of binding to modified histones, directly interacts with DDB1, the main component of the CUL4B-Ring E3 ligase complex (CRL4B), which is responsible for H2AK119 mono-ubiquitination (H2AK119ub1). We showed that PHF1, PRMT5-WDR77, and CRL4B reciprocally interact with one another and collaborate as a functional unit. Genome-wide analysis of PHF1/PRMT5/CUL4B targets identified a cohort of genes including E-cadherin and FBXW7, which are critically involved in cell growth and migration. We demonstrated that PHF1...Continue Reading

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Citations

Dec 19, 2019·Journal of Cellular and Molecular Medicine·Lu GeMin Xu
Jan 15, 2020·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Jakob HofvanderFredrik Mertens
Jul 18, 2020·Biochemical Society Transactions·Yan ShiPing Zhu
Sep 29, 2020·Briefings in Bioinformatics·Zerong WangYongchun Zuo
Dec 18, 2019·The Journal of Clinical Investigation·Christopher L NoblesFrederic D Bushman
Dec 31, 2020·Life Science Alliance·Baskar ChakrapaniArunkumar Dhayalan
Dec 15, 2020·Trends in Biochemical Sciences·Robert M VaughanScott B Rothbart
Aug 3, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Sidong CaiPeiqing Liu
Aug 23, 2021·Protein Science : a Publication of the Protein Society·Bruno César Feltes
Aug 21, 2021·Journal of Zhejiang University. Science. B·Chunhui Li, Chunhong Wang
Sep 15, 2021·The Biochemical Journal·Jocelyn F Chen, Qin Yan

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Datasets Mentioned

BETA
GSE84071
GSE32641
GSE54140
GSE36774
GSE35428
GSE17025
GSE25638

Methods Mentioned

BETA
transfection
immunoprecipitation
pull-down
in vitro transcription
Peptide Array
chip
PCR
xenograft
affinity purification
co-immunoprecipitation

Software Mentioned

Origin
Kinetics /
Active Motif
Biacore T200
Origene
ChIP

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