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Cofactor squelching: Artifact or fact?

Søren Fisker Schmidt1, Bjørk Ditlev Larsen1, Anne Loft1

  • 1Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230, Odense M, Denmark.

Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology
|June 9, 2016
PubMed
Summary
This summary is machine-generated.

Cofactor squelching, where transcription factors (TFs) compete for limited cofactors, may be a relevant mechanism for gene repression. Recent studies suggest this indirect repression impacts signal-dependent TFs at enhancers.

Keywords:
ChIP-seqcofactor redistributioncofactor squelchingsuper-enhancerstranscriptional repression

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Cofactor squelching, the competition among transcription factors (TFs) for limited cellular cofactors, has been a debated concept for decades.
  • Historically, evidence for cofactor squelching as a physiological mechanism for transcriptional repression has been limited, primarily stemming from reporter assay studies.

Purpose of the Study:

  • To re-evaluate the concept of cofactor squelching in light of recent genome-wide findings.
  • To explore the potential physiological relevance of cofactor squelching as a mechanism of transcriptional repression.

Main Methods:

  • Review of classical studies on cofactor squelching.
  • Analysis of recent genome-wide studies investigating TF binding and enhancer activity.
  • Discussion of TF cooperativity in hotspots and super-enhancers.

Main Results:

  • Recent genome-wide studies show signal-dependent TFs are often absent from repressed enhancers, supporting indirect repression mechanisms like squelching.
  • TF cooperativity in regulatory regions like hotspots and super-enhancers may increase sensitivity to cofactor squelching.

Conclusions:

  • Cofactor squelching is a plausible mechanism for indirect transcriptional repression.
  • TF binding dynamics and cooperativity at specific regulatory elements may render them susceptible to cofactor squelching.