Transcription inhibition

The formation of a transcriptionally active complex requires the interaction of all transcription cofactors with their respective specific DNA sequences. Once they have bound to their specific sequences, it is on these that the remaining elements of the complex that do not interact directly with the DNA are assembled (Chin 1995 Filardo 2002). The elements of the complex that do not come into direct contact with DNA have their own specificity of interaction with the remaining proteins of the complex. Therefore, they include important restrictions so that a fully active transcriptional complex can be assembled with difficulty on a receptor dimer that has incorrectly recognized a HRE. Indeed, an incorrect interaction can imply a noticeable degree of transcription inhibition. 

The ability of DNA-binding drugs to induce chromatin condensation calls for in-depth studies, because the biological consequence of chromatin condensation is its loss of transcriptional ability. Therefore it might be a mechanism of transcription inhibition by the reversible DNA binders. The first report in this line (Sen and Crothers, 1986) employed transient electric dichroism to study the ability of the drugs to induce folding of chromatin from the 10- to 30-nm fiber either by... 

The association of homopyrimidine homopurine stretches of duplex DNA are known as receptors for triplex formation by major groove association of a TFO. TFO recognition of duplex DNA can be exploited by inducing transcription inhibition, site-directed mutagenesis, or recombination. Another attractive feature... 

Pyruvate carboxylase PEP carboxykinase Fructose 1,6-bisphosphate Glucose 6-phosphatase Transcription inhibited... 

Delauney, A.J., Tabaeizadeh, Z. Verma, D.P.S. (1988). A stable bifunctional antisense transcript inhibiting gene expression in transgenic plants. Proceedings of the National Academy of Sciences (USA) 85, 4300-4. 

Dervan, P.B. (1997) Gene-specific transcription inhibition in vivo by designed ligands. FASEBJ., 11,2546. 

Manning FCR, Xu J, Patiemo SR. 1992. Transcriptional inhibition by carcinogenic chromate Relationship to DNA damage. Mol Carcinog 6 270-279. 

Accordingly, some effort has been devoted to studying the effects of cisplatin on transcription. In vitro experiments with RNA polymerases demonstrated that productive elongation activity was prematurely terminated by the whole spectrum of cisplatin-DNA adducts, but not by the /ran.y-DDP 1,3-intrastrand adducts [150-152], Selective bypass of trans-DDP adducts was also demonstrated in XPA cells, suggesting that repair of the DNA lesions did not contribute to differential transcription inhibition by the platinum compounds [153], In vivo, hormone-induced chromatin remodeling and subsequent transcription from the MMTV promoter was specifically inhibited by cisplatin [154], In this case, platinum adducts seemed to cause a decrease in the DNA binding of one of the transcription factors, NF1. Several chromatin-associated proteins, such as the linker histone protein HI or... 

As mentioned above, one consequence of stalled RNA polymerase II at a DNA adduct is activation of transcription-coupled repair [27], This effect may depend on the type of polymerase, however, since the removal of some types of DNA damage is slower from RNA-polymerase I transcribed ribosomal DNA than from a nuclear gene [160], The lower level of repair in the nucleolus could also reflect the influence of other transcription factors, such as the HMG-domain protein UBF, which bind to cisplatin-mod-ified DNA [145]. When HeLa cells were exposed to cisplatin at concentrations which did not seem to affect nuclear transcription, inhibition of rDNA gene expression was associated with the redistribution of UBF, along with other factors responsible for rRNA transcription [138], These observations indicate how cisplatin might exert a combination of effects. Transcription is stopped due to titration of essential factors by the platinum-DNA adducts, and the same proteins could shield the lesions from the repair activity. 

Burnett R, et al. DNA sequence-specific polyamides alleviate transcription inhibition associated with long GAA.TTC repeats in Friedreich s ataxia. Proc. Natl. Acad. Sci. U.S.A. 2006 103 11497. 

Transcriptional inhibition can also be achieved by targeting a sequence located within the gene itself using artificial DBDs... 

Ringheim GE, Szcepanik AM, Burgher KL, et al. Transcriptional inhibition of the P-amyloid precursor protein by interferon-gamma. Biochem Biophys Res Commun 1996 224 246-51. 

Polyether Monensin Actinomycin D C3 ochalasin B Cyclohcximide lonophore Inhibits DNA transcription Inhibits cell division Protein synthesis inhibitor... 

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