Loss of coactivation function in the SRC-1 null mutants may be partially compensated by increased expression of the closely relat-

1. M-J. Tsai nd B. W. O’Malley, Annu. Rev. Biochem. 63, 451 (1994). 2. M. Beato, P. Herrlich, G. Schutz, Cell 83, 851 (1995); D. J. Mangelsdorf et al., ibid., p. 835. 3. H. Shibata et al., Recent Prog. Horm. Res. 52, 141 (1997 ). 4. J. Wong, Y. B. Shi, A. P. Wolffe, Genes Dev. 9, 2696 (1995). 5. A. P. Wolffe and D. Pruss, Cell 84, 817 (1996). 6. H. Chen et al., ibid. 90, 569 (1997 ). 7. T. E. Spencer et al., Nature 389, 194 (1997 ). 8. G. Jenster et al., Proc. Natl. Acad. Sci. U.S.A. 94, 7879 (1997 ). 9. S. A. Onate, S. Y. Tsai, M-J. Tsai, B. W. O’Malley, Science 270, 1354 (1995). 10. Y. Kamei et al., Cell 85, 403 (1996). 11. A. Takeshita et al., Endocrinology 137, 3594 (1996). 12. J. J. Voegel, M. J. S. Heine, C. Zechel, P. Chambon, H. Gronemeyer, EMBO J. 15, 3667 (1996). 13. H. Hong, K. Kohli, A. Trivedi, D. L. Johnson, M. R. Stallcup, Proc. Natl. Acad. Sci. U.S.A. 93, 4948 (1996). 14. J. Torchia et al., Nature 387, 677 (1997 ). 15. H. Li, P. J. Gomes, J. D. Chen, Proc. Natl. Acad. Sci. U.S.A. 94, 8479 (1997 ). 16. S. L. Anzick et al., Science 277, 965 (1997 ). 17. The GLVP cassette encodes a transcriptional regulator composed of the activation domain of VP-16, the DNA binding domain of gal4, and the mutated ligand-binding domain of PR. This regulator can be activated only by a progesterone antagonist, RU486 [Y. Wang, J. Xu, T. Pierson, B. W. O’Malley, S. Y. Tsai, Gene Ther. 4, 432 (1997 )]. This RU486dependent transregulator could control a transgene containing a gal4-binding site. The GLVP regulator was incorporated in case the SRC-1 mutation resulted in a lethal phenotype. 18. D. M. Heery, E. Kalkhoven, S. Hoare, M. G. Parker, Nature 387, 733 (1997 ). 19. Y. Qiu et al., Genes Dev. 11, 1925 (1997 ). 20. J. Xu, S. Y. Tsai, M.-J. Tsai, B. W. O’Malley, unpublished data. 21. T. E. Spencer, S. Y. Tsai, M-J. Tsai, B. W. O’Malley, unpublished data. 22. J. P. Lydon et al., Genes Dev. 9, 2266 (1995). 23. D. B. Lubahn et al., Proc. Natl. Acad. Sci. U.S.A. 90, 11162 (1993). 24. K. S. Korach et al., Recent Prog. Horm. Res. 51, 159 (1996). 25. C. L. Smith, S. A. Onate, M-J. Tsai, B. W. O’Malley, Proc. Natl. Acad. Sci. U.S.A. 93, 8884 (1996). 26. Y. J. Topper and C. S. Freeman, Physiol. Rev. 60, 1049 (1980). 27. Phage clones were identified by screening a 129Sv mouse genomic DNA library with a human SRC-1 cDNA probe. Inserts were excised by Not I digestion and subcloned into pBluescript II SK plasmid (Stratagene). Regions corresponding to specific amino acid sequences were defined by sequencing or by hybridization with oligonucleotide probes. 28. We thank K. Bramlett and L. A. Hadsell for technical assistance; C. Funk, Y. Wang, Z-Q. Ma, F. A. Pereira, and N. McKenna for discussion; P. Soriano for the mouse genomic library; A. Bradley for ES cells; D. P. Edwards for the SRC-1 antibody; P. Chambon for the TIF2 cDNA; and J. D. Chen for the RAC3 cDNA. Supported by a NIH NRSA fellowship (J.X.) and NIH grants (B.W.O.).