Targeting of N-CoR and histone deacetylase 3 by the oncoprotein v-ErbA yields a chromatin infrastructure-dependent transcriptional repression pathway

Transcriptional repression by nuclear hormone receptors is thought to resul t from a unison of targeting chromatin modification and disabling the basal transcriptional machinery. We used Xenopus oocytes to compare silencing ef fected by the thyroid hormone receptor (TR) and its mutated version, the on coprotein v-ErbA, on partly and fully chromatinized TR-responsive templates in vivo, Repression by v-ErbA was not as efficient as that mediated by TR, was significantly more sensitive to histone deacetylase (HDAC) inhibitor t reatment and, unlike TR, v-ErbA required mature chromatin to effect repress ion. We find that both v-ErbA and TR can recruit the corepressor N-CoR, but , in contrast to existing models, show a concomitant enrichment for HDAC3 t hat occurs without an association with Sin3, HDAC1/ RPD3, Mi-2 or HDAC5. We propose a requirement for chromatin infrastructure in N-CoR/HDAC3-effected repression and suggest that the inability of v-ErbA to silence on partly c hromatinized templates may stem from its impaired capacity to interfere wit h basal transcriptional machinery function. In support of this notion, we f ind v-ErbA to be less competent than TR for binding to TFIIB in vitro and i n vivo.