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Molecular Endocrinology 13 (12): 2151-2162
Copyright © 1999 by The Endocrine Society

Constitutive Activation of Transcription and Binding of Coactivator by Estrogen-Related Receptors 1 and 2

Wen Xie, Heng Hong, Na N. Yang1, Richard J. Lin, Cynthia M. Simon, Michael R. Stallcup and Ronald M. Evans

Howard Hughes Medical Institute (W.X., R.M.E.) Gene Expression Laboratory (W.X., N.N.Y., R.J.L., C.M.S., R.M.E.) The Salk Institute for Biological Studies La Jolla, California 92037
Department of Pathology (H.H., M.R.S.) University of Southern California Los Angeles, California 90033

In this report, we demonstrate that, in contrast to most previously characterized nuclear receptors, hERR1 and hERR2 (human estrogen receptor-related protein 1 and -2) are constitutive activators of the classic estrogen response element (ERE) as well as the palindromic thyroid hormone response element (TREpal) but not the glucocorticoid response element (GRE). This intrinsically activated state of hERR1 and hERR2 resides in the ligand-binding domains of the two genes and is transferable to a heterologous receptor. In addition, we show that members of the p160 family of nuclear receptor coactivators, ACTR (activator of thyroid and retinoic acid receptors), GRIP1 (glucocorticoid receptor interacting protein 1), and SRC-1 (steroid receptor coactivator 1), potentiate the transcriptional activity by hERR1 and hERR2 in mammalian cells, and that both orphan receptors bind the coactivators in a ligand-independent manner. Together, these results suggest that hERR1 and hERR2 activate gene transcription through a mechanism different from most of the previously characterized steroid hormone receptors.




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