Cloning and characterization of a corepressor and potential component of the nuclear hormone receptor repression complex

Cloning and characterization of a corepressor and potential component of the nuclear hormone receptor repression complex

^*Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; and ^‡Howard Hughes Medical Institute, ^§Department and School of Medicine, and ^†Graduate Program in Biology, University of California at San Diego, La Jolla, CA 92093

Contributed by Michael G. Rosenfeld

Abstract

Nuclear hormone receptors are potent repressors of transcription in the unliganded state. We describe here the cloning of a nuclear receptor corepressor that we call SUN-CoR (Small Unique Nuclear receptor CoRepressor), which shows no homology to previously described nuclear hormone receptor corepressors, N-CoR, or SMRT. SUN-CoR is a highly basic, 16-kDa nuclear protein that is expressed at high levels in adult tissues and is induced during adipocyte and myogenic differentiation. SUN-CoR potentiates transcriptional repression by thyroid hormone receptor and RevErb in vivo, represses transcription when fused to a heterologous DNA binding domain, and interacts with RevErb as well as with thyroid hormone receptor in vitro. SUN-CoR also interacts with N-CoR and SMRT in vitro and with endogenous N-CoR in cells. We conclude that SUN-CoR is a corepressor and may function as an additional component of the complex involved in transcriptional repression by unliganded and orphan nuclear hormone receptors.

Footnotes

↵ ¶ To whom reprint requests should be addressed at: University of Pennsylvania School of Medicine, 611 CRB, 415 Curie Blvd., Philadelphia, PA 19104-6149. e-mail: lazar{at}mail.med.upenn.edu.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AF031426).
ABBREVIATIONS:

NHR,

nuclear hormone receptor;

TR,

thyroid hormone receptor;

DBD,

DNA binding domain;

HA,

hemagglutinin;

GST,

glutathione S-transferase