Transcription repression

Repression of genes is associated with reversal of this process under the control of histone deacetylases (HDACs). Deacetylation of histones increases the winding of DNA round histone residues, resulting in a dense chromatin structure and reduced access of transcription factors to their binding sites, thereby leading to repressed transcription of inflammatory genes. 

Certain DNA Elements Enhance or Repress Transcription of Eukaryotic Genes... 

KASS s u, PRUSS D and WOLFFE A p (1997) How does DNAmethylation repress transcription . Trends Genet, 13, 444-9. 

Hur M-W. Sp3 and Sp4 can repress transcription by competing with Spl for core cis-elements on the human ADH5/FDH minimal promoter. J Biol Chem 1999 274 20-28... 

Fig. 4. Domain structure of mammalian DNA methyltransferases. (a) The domain structure of the known DNA methyltransferases, depicting the conserved catalytic domain (dark box) and other identified domains. Conserved aminoacid motifs in the catalytic domain are shown in lighter shade of gray. (b) Schematic representation of the reported protein-protein interactions of Dnmtl with a number of regulatory proteins interactions that modulate Dnmtl methyitransferase activity (darker rectangles) or mediate methylation-independent transcriptional repression mechanisms (lighter rectangles). When Dnmtl represses transcription through its enzymatic activity, it has been described to interact with some proteins PCNA [37] and an oncogenic transcription factor PML-RAR [25]. Note that in the case of the PML-RAR transcription factor, histone deacetylase 1 (HDACl) is also bound to the complex. When Dnmtl represses transcription via methylation-independent pathways, it binds to HDACs either directly [34] or indirectly through other proteins the corepressor DMAPl [33], the retinoblastoma protein, and a gene-specific transcription factor [31].

MeCP2 Contains conserved MBD motif and a transcription repression domain Represses transcription from a methylated promoter in vitro and in vivo participates in several co-repressor complexes Sin3A/HDACl-2, NCoR/Ski, Rest/CoRest Expressed in somatic tissues and in embryonic stem (ES) cells co-localizes with heavily methylated satellite DNA in mouse cells... 

MBD2 together with MBD3 (previously known as MeCPl) are part of the Mi2/NuRD co-repressor complex [76,89]. So far, no molecular partner proteins have been identified for MBDl this protein has multiple splice variants and can repress transcription through HDAC-dependent, as well as HDAC-independent mechanisms [87,88]. 

As mentioned earlier, MeCP2 is not the only protein that associates with HD AC activities. Both MBD2 and MBDl repress transcription in histone deacetylation-dependent manner. Interestingly, MBD2 was found associated not only with class I histone deacetylases (HDACl and 2) from the Mi2/NuRD corepressor complex but also with class II histone deacetylases in the silencing mediator of retinoic and thyroid receptor (SMRT)/HDAC 5,7 complex [137]. 

Prelich, G. and Winston, F. (1993) Mutations that suppress the deletion of an upstream activating sequence in yeast involvement of a protein kinase and histone H3 in repressing transcription in vivo. Genetics 135, 665-676. 

Jones, P.L., Veenstra, G.J., Wade, P.A., Vermaak, D Kass, S.U., Landsberger, N Strouboulis, J. and Wolffe, A.P. (1998) Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nature Genetics, 19,187-191. 

Frescas, D., Guardavaccaro, D., Bassermann, F., Koyama-Nasu, R. and Pagano, M. (2007) JHDMIB/FBXLIO is a nucleolar protein that represses transcription of ribosomal RNA genes. Nature, 450, 309-313. 

Enzymes that are involved in steroid hormone biosynthesis or in steroid metabolism are also targets of anti-hormonal therapy. Recently, it was discovered that certain co-factors modulate the signalling of steroid hormone receptors in a tissue-selective fashion. By binding the receptor ligand complex, these co-activators and co-repressors are capable of either activating or repressing transcription, respectively [5j. 

Kass, S.U., Truss, D., and Wolffe, A.R (1997) How does DNA meth-ylatlon repress transcription Trends Genet 13 444 40. 

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