DISTINCT REQUIREMENTS FOR CHROMATIN ASSEMBLY IN TRANSCRIPTIONAL REPRESSION BY THYROID-HORMONE RECEPTOR AND HISTONE DEACETYLASE

Histone deacetylase and chromatin assembly contribute to the control o f transcription of the Xenopus TR beta A gene promoter by the heterodi mer of Xenopus thyroid hormone receptor and 9-cis retinoic acid recept or (TR-RXR), Addition of the histone deacetylase inhibitor Trichostati n A (TSA) relieves repression of transcription due to chromatin assemb ly following microinjection of templates into Xenopus oocyte nuclei, a nd eliminates regulation of transcription by TR-RXR. Expression of Xen opus RPD3p, the catalytic subunit of histone deacetylase, represses th e TR beta A promoter, but only after efficient assembly of the templat e into nucleosomes, In contrast, the unliganded TR-RXR represses templ ates only partially assembled into nucleosomes; addition of TSA also r elieves this transcriptional repression, This result indicates the dis tinct requirements for chromatin assembly in mediating transcriptional repression by the deacetylase alone, compared with those needed in th e presence of unliganded TR-RXR. In addition, whereas hormone-bound TR -RXR targets chromatin disruption as assayed through changes in minich romosome topology and loss of a regular nucleosomal ladder on micrococ cal nuclease digestion, addition of TSA relieves transcriptional repre ssion but does not disrupt chromatin, Thus, TR-RXR can facilitate tran scriptional repression in the absence of hormone through mechanisms in addition to recruitment of deacetylase, and disrupts chromatin struct ure through mechanisms in addition to the inhibition or release of dea cetylase.