Movatterモバイル変換

[0]ホーム
URL:

Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

Wiley full text link Wiley Free PMC article
Full text links

Actions

Review
.2010 Jun 1;126(11):2511-9.
doi: 10.1002/ijc.25181.

Transcription factor co-repressors in cancer biology: roles and targeting

Affiliations
Review

Transcription factor co-repressors in cancer biology: roles and targeting

Sebastiano Battaglia et al. Int J Cancer..

Abstract

Normal transcription displays a high degree of flexibility over the choice, timing and magnitude of mRNA expression levels that tend to oscillate and cycle. These processes allow for combinatorial actions, feedback control and fine-tuning. A central role has emerged for the transcriptional co-repressor proteins such as NCOR1, NCOR2/SMRT, CoREST and CTBPs, to control the actions of many transcriptional factors, in large part, by recruitment and activation of a range of chromatin remodeling enzymes. Thus, co-repressors and chromatin remodeling factors are recruited to transcription factors at specific promoter/enhancer regions and execute changes in the chromatin structure. The specificity of this recruitment is controlled in a spatial-temporal manner. By playing a central role in transcriptional control, as they move and target transcription factors, co-repressors act as a key driver in the epigenetic economy of the nucleus. Co-repressor functions are selectively distorted in malignancy, by both loss and gain of function and contribute to the generation of transcriptional rigidity. Features of transcriptional rigidity apparent in cancer cells include the distorted signaling of nuclear receptors and the WNTs/beta-catenin axis. Understanding and predicting the consequences of altered co-repressor expression patterns in cancer cells has diagnostic and prognostic significance, and also have the capacity to be targeted through selective epigenetic therapies.

PubMed Disclaimer

Figures

Figure 1
Figure 1. A model for the deregulation of co-repressors leading to stable targeted repression
Panel A. In normal systems the balance of co-activator (CoA) and co-repressor (CoR) expression are in dynamic equilibrium (left) such that they are rapidly recruited to and released from transcription factor (TF) complexes to control tightly the underlying epigenetic events. Such a dynamic choreography can give rise to patterns of mRNA expression that are alternating, or cycling. The net result is the rapidly responsive and alternating kinetics of mRNA expression (right).Panel B. Elevated CoR expression in malignancy limits the extent of the transcriptional cycle and reduces the peak height and accentuates the minima.Panel C. The sustained expression of CoRs generates a repressive chromatin environment that can selectively attract the CpG methylation machinery and lead to transcriptional silencing that is stably inherited and complete attenuation of transcriptional responsiveness.
See this image and copyright information in PMC

References

    1. Taverna SD, Li H, Ruthenburg AJ, Allis CD, Patel DJ. How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers. Nat Struct Mol Biol. 2007;14:1025–40. - PMC - PubMed
    1. Dobrzynski M, Bruggeman FJ. Elongation dynamics shape bursty transcription and translation. Proceedings of the National Academy of Sciences of the United States of America. 2009 - PMC - PubMed
    1. Degenhardt T, Rybakova KN, Tomaszewska A, Mone MJ, Westerhoff HV, Bruggeman FJ, Carlberg C. Population-level transcription cycles derive from stochastic timing of single-cell transcription. Cell. 2009;138:489–501. - PubMed
    1. Mohn F, Schubeler D. Genetics and epigenetics: stability and plasticity during cellular differentiation. Trends Genet. 2009;25:129–36. - PubMed
    1. Thorne JL, Campbell MJ, Turner BM. Transcription factors, chromatin and cancer. Int J Biochem Cell Biol. 2009;41:164–75. - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full text links
Wiley full text link Wiley Free PMC article
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

[8]ページ先頭
©2009-2026 Movatter.jp