title: PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression.
abstract: While reversible histone modifications are linked to an ever-expanding range of biological functions, the demethylases for histone H4 lysine 20 and their potential regulatory roles remain unknown. Here we report that the PHD and Jumonji C (JmjC) domain-containing protein, PHF8, while using multiple substrates, including H3K9me1/2 and H3K27me2, also functions as an H4K20me1 demethylase. PHF8 is recruited to promoters by its PHD domain based on interaction with H3K4me2/3 and controls G1-S transition in conjunction with E2F1, HCF-1 (also known as HCFC1) and SET1A (also known as SETD1A), at least in part, by removing the repressive H4K20me1 mark from a subset of E2F1-regulated gene promoters. Phosphorylation-dependent PHF8 dismissal from chromatin in prophase is apparently required for the accumulation of H4K20me1 during early mitosis, which might represent a component of the condensin II loading process. Accordingly, the HEAT repeat clusters in two non-structural maintenance of chromosomes (SMC) condensin II subunits, N-CAPD3 and N-CAPG2 (also known as NCAPD3 and NCAPG2, respectively), are capable of recognizing H4K20me1, and ChIP-Seq analysis demonstrates a significant overlap of condensin II and H4K20me1 sites in mitotic HeLa cells. Thus, the identification and characterization of an H4K20me1 demethylase, PHF8, has revealed an intimate link between this enzyme and two distinct events in cell cycle progression.
authors.affiliation: Howard Hughes Medical Institute, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.forename: Bogdan
authors.initials: B
authors.lastname: Tanasa
authors.forename: Oksana V
authors.initials: OV
authors.lastname: Tyurina
authors.forename: Tian Yuan
authors.initials: TY
authors.lastname: Zhou
authors.forename: Reto
authors.initials: R
authors.lastname: Gassmann
authors.forename: Wei Ting
authors.initials: WT
authors.lastname: Liu
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Ohgi
authors.forename: Chris
authors.initials: C
authors.lastname: Benner
authors.forename: Ivan
authors.initials: I
authors.lastname: Garcia-Bassets
authors.forename: Aneel K
authors.initials: AK
authors.lastname: Aggarwal
authors.forename: Arshad
authors.initials: A
authors.lastname: Desai
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Dorrestein
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Glass
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rosenfeld
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D056466:Histone Demethylases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D051863:Host Cell Factor C1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; D006657:Histones; D051863:Host Cell Factor C1; D046912:Multiprotein Complexes; C000589016:NCAPG2 protein, human; D014157:Transcription Factors; C108312:condensin complexes; D056466:Histone Demethylases; C511934:PHF8 protein, human; D011495:Histone-Lysine N-Methyltransferase; C470730:KMT5A protein, human; C526068:Setd1A protein, human; D000251:Adenosine Triphosphatases; D008239:Lysine