Corepressive Action of CBP on Androgen Receptor Transactivation in Pericentric Heterochromatin in a Drosophila Experimental Model System

• DOI: 10.1128/mcb.02123-07
• Publication Date: 2008-12-16T01:55:09Z
• Authors: Yue Zhao; Ken-ichi Takeyama; Shun Sawatsubashi; Saya Ito; Eriko Suzuki; Kaoru Yamagata; Masahiko Tanabe; Shuhei Kimura; Sally Fujiyama; Takashi Ueda; Takuya Murata; Hiroyuki Matsukawa; Yuko Shirode; Alexander P. Kouz...; Feng Li; Testuya Tabata; Shigeaki Kato
• Keywords: Euchromatin; Corepressor; Heterochromatin protein 1; Chromatin immunoprecipitation

Ligand-bound nuclear receptors (NR) activate transcription of the target genes. This activation is coupled with histone modifications and chromatin remodeling through function various coregulators. However, nature dependence a NR coregulator action on presence environment at genes unclear. To address this issue, we have developed modified position effect variegation experimental model system that includes an androgen-dependent reporter transgene inserted into either pericentric heterochromatin region or euchromatic Drosophila chromosome. Human androgen receptor (AR) its constitutively active truncation mutant (AR AF-1) were transcriptionally functional in both chromosomal regions. Predictably, level AR-induced transactivation was lower heterochromatin. In genetic screening for AR AF-1 coregulators, CREB binding protein (dCBP) found to corepress whereas it led coactivation area. Mutations Sir2 acetylation sites deletion CBP acetyltransferase domain abrogated dCBP corepressive heterochromatic areas vivo. Such corepressor observed silent promoter gene cultured mammalian cells. Thus, our findings suggest coregulators may depend state loci.