Identification and characterization of novel complexes controling chromatin structure

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Gene expression is controlled through chromatin remodeling and histon modifications. Such chromatin structure rearrangement is conducted by a number of nuclear complexes composed of multiple subunits. In the present study, to identify and characterize the nuclear complexes to support hormone-induced transcriptional controls by nuclear receptors, a biochemical purification of complexes associating with sex steroid hormone receptors. By such biochemical screening, we could identify several complexes containing histone modifying enzymes. One of the complex was a novel complex containing histone acetyltransferase to coactivate estrogen receptor, while another complex was a histone deacetylase to corepress estrogen and androgen receptors. Moreover, we could identify a novel ubiquitin E3 ligase to degrate sex steroid receptor proteins. Previously, we had shown that activated dioxin receptor(AhR) by ligand binding coactivates unliganded sex steroid receptors in transcriptional controls through direct receptor-receptor protein interaction (Ohtake et al., Nature, 423, 545-550, 2003). However, transrepression of liganded steroid receptors by AhR was still under investigation. By biochemical purification of a complex containing AhR and sex steroid receptors, we have demonstrated that liganded AhR is ligand- dependent E3 ubiquitin ligase to degrate steroid receptors, thereby counteracting biological actions of sex steroid hormones (Ohtake et al., Nature, 446, 562-566, 2007).