Article

Gene silencing by the thyroid hormone receptor.

Genetic Institute, Justus-Liebig-University, Heinrich-Buff-Ring 58-62, D-35392 Giessen, Germany.
Molecular and Cellular Endocrinology (impact factor: 4.19). 01/2004; 213(1):13-22. DOI:10.1016/j.mce.2003.10.026 pp.13-22
Source: PubMed

ABSTRACT The thyroid hormone receptors (TR) are able to bind DNA and to repress transcription in the absence of thyroid hormone. This repression function is an important feature of TRs as aberrant silencing can lead to severe diseases and developmental abnormalities. TR utilizes different mechanisms to achieve repression of target genes including the recruitment of cofactors called corepressors and interference with the basal transcriptional machinery. Recent studies have revealed an important role of chromatin in TR silencing involving different histone modifications and the responsible enzymes. Furthermore, the transcriptional properties of TR depend on the type of the TR DNA-binding elements. This review will focus on the molecular basis of gene silencing by TR and diseases caused by aberrant functioning.

0 0
 · 
0 Bookmarks
 · 
21 Views
  • Source
    Article: The highly conserved region of the co-repressor Sin3A functionally interacts with the co-repressor Alien.
    Udo Moehren, Uwe Dressel, Christina A Reeb, Sami Väisänen, Thomas W Dunlop, Carsten Carlberg, Aria Baniahmad
    [show abstract] [hide abstract]
    ABSTRACT: The Sin3 proteins are evolutionarily conserved co-repressors (CoR) that function as mediators of gene repression for a variety of transcriptional silencers. The paired amphipathic helices of Sin3A were identified and studied as protein-protein interacting domains. Previously we have shown the interaction of Sin3A with the CoR Alien in vivo and in vitro. Here, we show that Alien and Sin3A reside together in vivo with the vitamin D3 receptor on the human 24-hydroxylase (CYP24) promoter containing vitamin D3 response elements by chromatin immunoprecipitation. We delineated and characterized the interaction domains of Sin3A with Alien. Interestingly, the highly conserved region (HCR) of Sin3A, which has not yet been functionally characterized, interacts with Alien. The HCR encompasses only 134 amino acids, shares more than 80% identity with Sin3B and binds to the N-terminus of Alien, which harbours a transferable silencing function. Functionally, co-expression of Sin3A enhances Alien-mediated gene repression and overexpression of the HCR alone leads to the inhibition of Alien-mediated repression and to the induction of the endogenous CYP24 promoter. Our results therefore indicate a novel functional role of the Sin3 HCR and give novel insights into Alien-mediated gene repression.
    Nucleic Acids Research 02/2004; 32(10):2995-3004. · 8.03 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

basal transcriptional machinery
 
bind DNA
 
chromatin
 
corepressors
 
developmental abnormalities
 
different histone modifications
 
Recent studies
 
repress transcription
 
responsible enzymes
 
severe diseases
 
target genes
 
thyroid hormone
 
thyroid hormone receptors
 
TR
 
TR DNA-binding elements
 
TR utilizes different mechanisms
 
transcriptional properties
 
TRs
 

Maren Eckey