Here's a recent paper (last month) involving some of our favorite players (heterduplexes with RXR and TR, thyroid hormone receptor) as well as histone deacetylases and effects of an inhibitor (Trichostatin A):
EMBO J 1998 Jan 15;17(2):520-534
Distinct requirements for chromatin assembly in
transcriptional repression by thyroid hormone receptor
and histone deacetylase.
Wong J, Patterton D, Imhof A, Guschin D, Shi YB, Wolffe AP
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development,
Bethesda, MD 20892-5431, USA.
Histone deacetylase and chromatin assembly contribute to the control of transcription of the
Xenopus TRbetaA gene promoter by the heterodimer of Xenopus thyroid hormone receptor and
9-cis retinoic acid receptor (TR-RXR). Addition of the histone deacetylase inhibitor Trichostatin A
(TSA) relieves repression of transcription due to chromatin assembly following microinjection of
templates into Xenopus oocyte nuclei, and eliminates regulation of transcription by TR-RXR.
Expression of Xenopus RPD3p, the catalytic subunit of histone deacetylase, represses the TRbetaA
promoter, but only after efficient assembly of the template into nucleosomes. In contrast, the
unliganded TR-RXR represses templates only partially assembled into nucleosomes; addition of
TSA also relieves this transcriptional repression. This result indicates the distinct requirements for
chromatin assembly in mediating transcriptional repression by the deacetylase alone, compared with
those needed in the presence of unliganded TR-RXR. In addition, whereas hormone-bound
TR-RXR targets chromatin disruption as assayed through changes in minichromosome topology and
loss of a regular nucleosomal ladder on micrococcal nuclease digestion, addition of TSA relieves
transcriptional repression but does not disrupt chromatin. Thus, TR-RXR can facilitate
transcriptional repression in the absence of hormone through mechanisms in addition to recruitment
of deacetylase, and disrupts chromatin structure through mechanisms in addition to the inhibition or
release of deacetylase.
PMID: 9430643, UI: 98094373 |
