Abstract
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.
Highlights
18166 JOURNAL OF BIOLOGICAL CHEMISTRY scription factors
The known NR co-activator SRC-1, and several transcription-related proteins were identified. Among these factors we focused on a protein previously described as Double PHD Fingers family 2 (DPF2)
DPF2 Suppresses the Transactivation Function of ERR␣—To examine the transcriptional function of DPF2, we generated a chimeric protein in which DPF2 was fused to the yeast GAL4 DNA binding domain and examined the transactivation function of DPF2 with a luciferase reporter assay in mouse myoblast C2C12 cells
Summary
18166 JOURNAL OF BIOLOGICAL CHEMISTRY scription factors. For most members of the NR superfamily, the transcriptional function is dependent on binding of lipophilic ligands such as steroid hormones and fat-soluble vitamins. DPF2 Recognizes Histones and Suppresses ERR␣ through HDAC1 logic role of ERR␣, a number of ERR␣ target genes have been identified [15], and transcriptional function was shown to depend on chromatin environment of the promoters. We biochemically identified DPF2 [21] as an ERR␣ interacting protein and characterized its co-repressor function for ERR␣.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
