Cofactor squelching

Artifact or fact?

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Cofactor squelching is the term used to describe competition between transcription factors (TFs) for a limited amount of cofactors in a cell with the functional consequence that TFs in a given cell interfere with the activity of each other. Since cofactor squelching was proposed based primarily on reporter assays some 30 years ago, it has remained controversial, and the idea that it could be a physiologically relevant mechanism for transcriptional repression has not received much support. However, recent genome-wide studies have demonstrated that signal-dependent TFs are very often absent from the enhancers that are acutely repressed by those signals, which is consistent with an indirect mechanism of repression such as squelching. Here we review these recent studies in the light of the classical studies of cofactor squelching, and we discuss how TF cooperativity in so-called hotspots and super-enhancers may sensitize these to cofactor squelching.

OriginalsprogEngelsk
TidsskriftBioEssays
Vol/bind38
Udgave nummer7
Sider (fra-til)618-626
ISSN0265-9247
DOI
StatusUdgivet - jul. 2016

Fingeraftryk

Artifacts
Transcription Factors
Assays
Genes

Citer dette

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Cofactor squelching : Artifact or fact? / Schmidt, Søren Fisker; Larsen, Bjørk Ditlev; Loft, Anne; Mandrup, Susanne.

I: BioEssays, Bind 38, Nr. 7, 07.2016, s. 618-626.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Cofactor squelching

T2 - Artifact or fact?

AU - Schmidt, Søren Fisker

AU - Larsen, Bjørk Ditlev

AU - Loft, Anne

AU - Mandrup, Susanne

N1 - © 2016 WILEY Periodicals, Inc.

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Y1 - 2016/7

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AB - Cofactor squelching is the term used to describe competition between transcription factors (TFs) for a limited amount of cofactors in a cell with the functional consequence that TFs in a given cell interfere with the activity of each other. Since cofactor squelching was proposed based primarily on reporter assays some 30 years ago, it has remained controversial, and the idea that it could be a physiologically relevant mechanism for transcriptional repression has not received much support. However, recent genome-wide studies have demonstrated that signal-dependent TFs are very often absent from the enhancers that are acutely repressed by those signals, which is consistent with an indirect mechanism of repression such as squelching. Here we review these recent studies in the light of the classical studies of cofactor squelching, and we discuss how TF cooperativity in so-called hotspots and super-enhancers may sensitize these to cofactor squelching.

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