Scaffold Attachment Factor SAFB1 Suppresses Estrogen Receptor α-Mediated Transcription in Part via Interaction with Nuclear Receptor Corepressor

Activity of the estrogen receptor (ER) is regulated through interaction with coactivators and corepressors. These proteins are present in large complexes, suggesting functional interactions among various cofactors. Scaffold attachment factors B1 and B2 (SAFB1/2) and nuclear receptor corepressor (N-CoR) function as ERα corepressors—they directly interact with ERα, and repress transcription via repression domains. We asked the question whether SAFB1/2 and N-CoR could directly interact with each other, and whether this interaction results in altered repressive activities. Employing coimmunoprecipitation, cofractionation, and colocalization experiments, we have shown that SAFB1/2 interact with the nuclear receptor corepressor N-CoR. This interaction was direct, and was mediated in vitro and in vivo through the C-terminal region of SAFB1 (amino acids 600–915 and the N-terminal region of N-CoR (amino acids 1–373). Decrease of SAFB1 or N-CoR expression by small interfering RNA resulted in an increase of the estr...