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PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression.

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.

Pubmed ID: 20622854


  • Liu W
  • Tanasa B
  • Tyurina OV
  • Zhou TY
  • Gassmann R
  • Liu WT
  • Ohgi KA
  • Benner C
  • Garcia-Bassets I
  • Aggarwal AK
  • Desai A
  • Dorrestein PC
  • Glass CK
  • Rosenfeld MG



Publication Data

July 22, 2010

Associated Grants

  • Agency: NCI NIH HHS, Id: R01 CA097134
  • Agency: NCI NIH HHS, Id: R01 CA097134-09
  • Agency: NIDDK NIH HHS, Id: R01 DK018477
  • Agency: NIDDK NIH HHS, Id: R01 DK018477-35
  • Agency: NIDDK NIH HHS, Id: R01 DK039949
  • Agency: NIDDK NIH HHS, Id: R01 DK039949-18
  • Agency: NHLBI NIH HHS, Id: R01 HL065445
  • Agency: NINDS NIH HHS, Id: R01 NS034934
  • Agency: NINDS NIH HHS, Id: R01 NS034934-21
  • Agency: NIDDK NIH HHS, Id: R37 DK039949
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Adenosine Triphosphatases
  • Cell Cycle
  • Cell Line
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • HeLa Cells
  • Histone Demethylases
  • Histone-Lysine N-Methyltransferase
  • Histones
  • Host Cell Factor C1
  • Humans
  • Lysine
  • Methylation
  • Multiprotein Complexes
  • Phosphorylation
  • Promoter Regions, Genetic
  • Protein Structure, Tertiary
  • Transcription Factors