Target specificities of estrogen receptor-related receptors: analysis of binding sequences and identification of Rb1-inducible coiled-coil 1 (Rb1cc1) as a target gene.
Estrogen receptor-related receptors (ERRs) are orphan members of the nuclear receptor superfamily. A single AGGTCA sequence element preceded by three conserved nucleotides has been identified as a specific recognition motif of ERRs. Here we performed systematic analyses of target sequences on all three ERR subtypes, alpha, beta and gamma. In electrophoretic gel-mobility shift assay and transcriptional reporter assays, they exhibited similar patterns of recognition specificities, showing extremely broad ranges of target sequences. We searched a mouse promoter database for a gene carrying possible ERR-binding sequences. The Rb-1 inducible coiled-coil 1 (Rb1cc1) gene was found to contain two putative ERR binding elements, named response element (RE)-1 and RE-2, in the promoter region. In gene reporter assays, RE-2, but not RE-1, functioned as an effective cis-regulatory element for transactivation by ERRalpha in the presence of a coactivator, peroxisome proliferator-activated receptor gamma coactivator-1alpha. Mutational analyses suggested that RE-2 is recognized by ERRalpha partly as a monovalent element, but also as a direct repeat motif separated by four spacer nucleotides. In vivo binding of ERRalpha to the Rb1cc1 promoter region was confirmed by the chromatin immunoprecipitation assay. Thus, Rb1cc1 is a target gene of ERRalpha, driven by a novel type of recognition sequence.
Graduate School of Life Science, University of Hyogo, Kamigori, Hyogo, Japan.
Mst Hasina
MH
Akter
Tokuhiro
T
Chano
Hidetoshi
H
Okabe
Tomohiro
T
Yamaguchi
Fumiko
F
Hirose
Takashi
T
Osumi
D000818:Animals; D000071183:Autophagy-Related Proteins; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013379:Substrate Specificity; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000235:genetics; D000097983:ERRalpha Estrogen-Related Receptor
D000071183:Autophagy-Related Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011960:Receptors, Estrogen; D015534:Trans-Activators; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor; C485290:Ppargc1a protein, mouse; C428743:Rb1cc1 protein, mouse