Double PHD fingers protein DPF2 recognizes acetylated histones and suppresses the function of estrogen-related receptor alpha through histone deacetylase 1.
Estrogen-related receptor alpha (ERRalpha) is a member of the nuclear receptor superfamily and regulates many physiological functions, including mitochondrial biogenesis and lipid metabolism. ERRalpha enhances the transactivation function without endogenous ligand by associating with coactivators such as peroxisome proliferator-activated receptor gamma coactivator 1 alpha and beta (PGC-1alpha and -beta) and members of the steroid receptor coactivator family. However, the molecular mechanism by which the transactivation function of ERRalpha is converted from a repressive state to an active state is poorly understood. Here we used biochemical purification techniques to identify ERRalpha-associated proteins in HeLa cells stably expressing ERRalpha. Interestingly, we found that double PHD fingers protein DPF2/BAF45d suppressed PGC-1alpha-dependent transactivation of ERRalpha by recognizing acetylated histone H3 and associating with HDAC1. DPF2 directly bound to ERRalpha 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 ERRalpha. These results show that DPF2 acts as a nuclear receptor-selective co-repressor for ERRalpha by associating with both acetylated histone H3 and HDAC1.
Matsuyama
Reiko
R
Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-0032, Japan.
Takada
Ichiro
I
Yokoyama
Atsushi
A
Fujiyma-Nakamura
Sally
S
Tsuji
Naoya
N
Kitagawa
Hirochika
H
Fujiki
Ryoji
R
Kim
Misun
M
Kouzu-Fujita
Madoka
M
Yano
Tetsu
T
Kato
Shigeaki
S
D000107:Acetylation; D000818:Animals; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D056284:Histone Deacetylase 1 / Q000737:chemistry* / Q000235:genetics; D006657:Histones / Q000737:chemistry; D006801:Humans; D051379:Mice; D009154:Mutation; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000737:chemistry*; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D000097983:ERRalpha Estrogen-Related Receptor
D004268:DNA-Binding Proteins; D056284:Histone Deacetylase 1; D006657:Histones; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D012097:Repressor Proteins; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor; C113581:DPF2 protein, human; C550323:DPF2 protein, mouse
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