Double PHD fingers protein DPF2 recognizes acetylated histones and suppresses the function of estrogen-related receptor α through histone deacetylase 1

Reiko Matsuyama, Ichiro Takada, Atsushi Yokoyama, Sally Fujiyma-Nakamura, Naoya Tsuji, Hirochika Kitagawa, Ryoji Fujiki, Misun Kim, Madoka Kouzu-Fujita, Tetsu Yano, Shigeaki Kato

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17 Citations (Scopus)

Abstract

Estrogen-related receptor α (ERRα) is a member of the nuclear receptor superfamily and regulates many physiological functions, including mitochondrial biogenesis and lipid metabolism. ERRα enhances the transactivation function without endogenous ligand by associating with coactivators such as peroxisome proliferator-activated receptor γ coactivator 1 α and β (PGC-1αand -β) and members of the steroid receptor coactivator family. However, the molecular mechanism by which the transactivation function of ERRα is converted from a repressive state to an active state is poorly understood. Here we used biochemical purification techniques to identify ERRα-associated proteins in HeLa cells stably expressing ERRα. Interestingly, we found that double PHD fingers protein DPF2/BAF45d suppressed PGC-1α-dependent transactivation of ERRα by recognizing acetylated histone H3 and associating with HDAC1. DPF2 directly bound to ERRα and suppressed the transactivation function of nuclear receptors such as androgen receptor. DPF2 was recruited to ERR target gene promoters in myoblast cells, and knockdown of DPF2 derepressed the level of mRNA expressed by target genes of ERRα. These results show that DPF2 acts as a nuclear receptor-selective co-repressor for ERRα by associating with both acetylated histone H3 and HDAC1.

Original languageEnglish
Pages (from-to)18166-18176
Number of pages11
JournalJournal of Biological Chemistry
Volume285
Issue number24
DOIs
Publication statusPublished - 2010 Jun 11

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Matsuyama, R., Takada, I., Yokoyama, A., Fujiyma-Nakamura, S., Tsuji, N., Kitagawa, H., Fujiki, R., Kim, M., Kouzu-Fujita, M., Yano, T., & Kato, S. (2010). Double PHD fingers protein DPF2 recognizes acetylated histones and suppresses the function of estrogen-related receptor α through histone deacetylase 1. Journal of Biological Chemistry, 285(24), 18166-18176. https://doi.org/10.1074/jbc.M109.077024