Inhibition of oestrogen receptor activity by the co-repressor HET/SAF-B is relieved by blockade of histone deacetylase activity

Abstract

The oestrogen receptor (ER) is a member of a superfamily of nuclear transcription factors. When the ER binds oestrogen it undergoes a conformational change that results in dimerisation, binding to specific elements of DNA, and finally altered gene transcription [ 1 Smith D.F. Toft D.O. Steroid receptors and their associated proteins. Mol. Endocrinol. 1993; 7: 4-11 Crossref PubMed Scopus (49) Google Scholar ]. While this model of ER action has held true for the last 30 years, a more complete understanding has revealed that activation of the ER is extremely complex, with regulation by a diverse set of signals and nuclear factors. A poorly described modulator of hormone action is the nuclear matrix, which is a dynamic structure involved in DNA replication, transcription, repair and RNA processing [ 2 Bird R.C. Stein G.S. Lian J.B. Stein J.L. Nuclear structure and gene expression. in: Buetow D.E. Cameron I.L. Padilla G.M. Zimmerman A.M. Cell Biology A Series of Monographs. Academic Press, New York1997 Google Scholar ]. A role for the nuclear matrix in hormone receptor action was postulated many years ago but only recently have specific nuclear matrix proteins been characterised which directly bind to hormone receptors and modulate their activity [ 3 Barrett T.J. Spelsberg T.C. Nuclear matrix and steroid hormone action. Vitamins and Hormones. 1999; 55: 127-163 Crossref PubMed Scopus (17) Google Scholar , 4 Eggert M. Michel J. Schneider S. et al. The glucocorticoid receptor is associated with the RNA-binding nuclear matrix protein hnRNP U. J. Biol. Chem. 1997; 272: 28471-28478 Crossref PubMed Scopus (73) Google Scholar ].