title: Scaffold attachment factor B (SAFB)1 and SAFB2 cooperatively inhibit the intranuclear mobility and function of ERα.
abstract: Estrogen receptor alpha (ERα) plays a key role in physiological and pathophysiological processes as a ligand-activated transcriptional factor that is regulated by cofactors. ERα-mediated transcriptional regulation is closely correlated with the mobility of ERα in the nucleus in association with the nuclear matrix, the framework for nuclear events including transcription. However, the relationship between ERα mobility and the cofactors of ERα is unclear. Scaffold attachment factor B1 (SAFB1) and its paralog SAFB2 are nuclear matrix binding proteins that have been characterized as ERα corepressors. Here, using chimeric fluorescent proteins (FPs), we show that SAFB1 and SAFB2 colocalize with ERα in the nucleus of living cells after 17β-estradiol (E2) treatment. Co-immunoprecipitation (co-IP) experiments indicated that ERα interacts with both SAFB1 and SAFB2 in the presence of E2. Fluorescence recovery after photobleaching analysis revealed that SAFB1 and SAFB2 each decrease ERα mobility, and interestingly, coexpression of SAFB1 and SAFB2 causes a synergistic reduction in ERα dynamics under E2 treatment. In accordance with these mobility changes, ERα-mediated transcription and proliferation are cooperatively inhibited by SAFB1 and SAFB2. These results indicate that SAFB1 and SAFB2 are crucial repressors for ERα dynamics in association with the nuclear matrix and that their synergistic regulation of ERα mobility is sufficient for inhibiting ERα function.
authors.affiliation: Department of Anatomy and Neurobiology, Kyoto Prefectural University of Medicine, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Matsuda
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kawata
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002521:Cercopithecus; D002522:Chlorocebus aethiops; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; D036961:Matrix Attachment Region Binding Proteins; D034521:Nuclear Matrix-Associated Proteins; D011960:Receptors, Estrogen; C109132:SAFB protein, human; C486369:SAFB2 protein, human