TY - JOUR
T1 - PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression
AU - Liu, Wen
AU - Tanasa, Bogdan
AU - Tyurina, Oksana V.
AU - Zhou, Tian Yuan
AU - Gassmann, Reto
AU - Liu, Wei Ting
AU - Ohgi, Kenneth A.
AU - Benner, Chris
AU - Garcia-Bassets, Ivan
AU - Aggarwal, Aneel K.
AU - Desai, Arshad
AU - Dorrestein, Pieter C.
AU - Glass, Christopher K.
AU - Rosenfeld, Michael G.
N1 - Funding Information:
Acknowledgements We thank W. Herr for providing HCF-1 and SET1A antibody; A. C. Wilson for providing pCGN-GAL4-HA-HCF-1(N1011) and pCGN-GAL4-HA-HCF-1(C600) expression vectors; A. I. Lamond for providing YFP-HCF-1 expression vector; K. Wang for experimental assistance; J. Nand for assistance with the ChIP-Seq data analysis; C. Nelson for cell culture assistance; J. Hightower and D. Benson for assistance with figure and manuscript preparation and the UCSD BIOGEM laboratory for RNA profiling. M.G.R. is an Investigator with the Howard Hughes Medical Institute. This work was supported by grants from NIH and NCI to A.K.A., P.C.D., C.K.G, A.D. and M.G.R. and from DOD and PCF to M.G.R. We apologize that we were not able to cite all the studies in the primary references characterizing PHF8 family enzymatic activities while our work was under review, due to reference limitation.
PY - 2010/7/23
Y1 - 2010/7/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77954954200&partnerID=8YFLogxK
U2 - 10.1038/nature09272
DO - 10.1038/nature09272
M3 - Article
C2 - 20622854
AN - SCOPUS:77954954200
SN - 0028-0836
VL - 466
SP - 508
EP - 512
JO - Nature
JF - Nature
IS - 7305
ER -