Cofactor squelching: Artifact or fact?
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.
Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230, Odense M, Denmark.
Søren Fisker
SF
Schmidt
Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230, Odense M, Denmark.
Bjørk Ditlev
BD
Larsen
Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230, Odense M, Denmark.
Anne
A
Loft
Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230, Odense M, Denmark.
Susanne
S
Mandrup
D000818:Animals; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D056890:Eukaryota / Q000235:genetics / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D014157:Transcription Factors; D004247:DNA
ChIP-seq; cofactor redistribution; cofactor squelching; super-enhancers; transcriptional repression