1. Ligand-controlled interaction of histone acetyltransferase binding to ORC-1 (HBO1) with the N-terminal transactivating domain of progesterone receptor induces steroid receptor coactivator 1-dependent coactivation of transcription
- Author
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Georgiakaki, M. (Maria), Blok, L.J. (Leen), Milgrom, R. (Roni), Lombès, M. (Marc), Guiochon-Mantel, A. (Anne), Loosfelt, H. (Hugues), Chabbert-Buffet, N. (Nathalie), Dasen, B. (Boris), Meduri, G. (Geri), Wenk, S. (Sandra), Rajhi, L. (Leila), Amazit, L. (Larbi), Chauchereau, A. (Anne), Burger, C.W. (Curt), Georgiakaki, M. (Maria), Blok, L.J. (Leen), Milgrom, R. (Roni), Lombès, M. (Marc), Guiochon-Mantel, A. (Anne), Loosfelt, H. (Hugues), Chabbert-Buffet, N. (Nathalie), Dasen, B. (Boris), Meduri, G. (Geri), Wenk, S. (Sandra), Rajhi, L. (Leila), Amazit, L. (Larbi), Chauchereau, A. (Anne), and Burger, C.W. (Curt)
- Abstract
Modulators of cofactor recruitment by nuclear receptors are expected to play an important role in the coordination of hormone-induced transactivation processes. To identify such factors interacting with the N-terminal domain (NTD) of the progesterone receptor (PR), we used this domain as bait in the yeast Sos-Ras two-hybrid system. cDNAs encoding the C-terminal MYST (MOZ-Ybf2/Sas3-Sas2-Tip60 acetyltransferases) domain of HBO1 [histone acetyltransferase binding to the origin recognition complex (ORC) 1 subunit], a member of the MYST acetylase family, were thus selected from a human testis cDNA library. In transiently transfected CV1 cells, the wildtype HBO1 [611 amino acids (aa)] enhanced transcription mediated by steroid receptors, notably PR, mineralocorticoid receptor, and glucocorticoid receptor, and strongly induced PR and estrogen receptor coactivation by steroid receptor coactivator 1a (SRC-1a). As assessed by two-hybrid and glutathione-S-transferase pull-down assays, the HBO1 MYST acetylase domain (aa 340-611) interacts mainly with the NTD, and also contacts the DNA-binding domain and the hinge domains of hormone-bound PR. The HBO1 N-terminal region (aa 1-340) associates additionally with PR ligand-binding domain (LBD). HBO1 was found also to interact through its NTD with SRC-1a in the absence of steroid receptor. The latter coassociation enhanced specifically activation function 2 activation function encompassed in the LBD. Conversely, the MYST acetylase domain specifically enhanced SRC-1 coupling with PR NTD, through a hormone-dependent mechanism. In human embryonic kidney 293 cells expressing human PRA or PRB, HBO1 raised selectively an SRC-1-dependent response of PRB but failed to regulate PRA activity. We show that HBO1 acts through modification of an LBD-controlled structure present in the N terminus of PRB leading to the modulation of SRC-1 functional coupling with activation function 3-mediated transcription. Importantly, real-time RT-PCR analysis als
- Published
- 2006
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