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A test of the pioneer factor hypothesis using ectopic liver gene activation

The pioneer factor hypothesis (PFH) states that pioneer factors (PFs) are a subclass of transcription factors (TFs) that bind to and open inaccessible sites and then recruit non-pioneer factors (non-PFs) that activate batteries of silent genes. The PFH predicts that ectopic gene activation requires...

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Detalles Bibliográficos
Autores principales: Hansen, Jeffrey L, Loell, Kaiser J, Cohen, Barak A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8849321/
https://www.ncbi.nlm.nih.gov/pubmed/34984978
http://dx.doi.org/10.7554/eLife.73358
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author Hansen, Jeffrey L
Loell, Kaiser J
Cohen, Barak A
author_facet Hansen, Jeffrey L
Loell, Kaiser J
Cohen, Barak A
author_sort Hansen, Jeffrey L
collection PubMed
description The pioneer factor hypothesis (PFH) states that pioneer factors (PFs) are a subclass of transcription factors (TFs) that bind to and open inaccessible sites and then recruit non-pioneer factors (non-PFs) that activate batteries of silent genes. The PFH predicts that ectopic gene activation requires the sequential activity of qualitatively different TFs. We tested the PFH by expressing the endodermal PF FOXA1 and non-PF HNF4A in K562 lymphoblast cells. While co-expression of FOXA1 and HNF4A activated a burst of endoderm-specific gene expression, we found no evidence for a functional distinction between these two TFs. When expressed independently, both TFs bound and opened inaccessible sites, activated endodermal genes, and ‘pioneered’ for each other, although FOXA1 required fewer copies of its motif for binding. A subset of targets required both TFs, but the predominant mode of action at these targets did not conform to the sequential activity predicted by the PFH. From these results, we hypothesize an alternative to the PFH where ‘pioneer activity’ depends not on categorically different TFs but rather on the affinity of interaction between TF and DNA.
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spelling pubmed-88493212022-02-17 A test of the pioneer factor hypothesis using ectopic liver gene activation Hansen, Jeffrey L Loell, Kaiser J Cohen, Barak A eLife Chromosomes and Gene Expression The pioneer factor hypothesis (PFH) states that pioneer factors (PFs) are a subclass of transcription factors (TFs) that bind to and open inaccessible sites and then recruit non-pioneer factors (non-PFs) that activate batteries of silent genes. The PFH predicts that ectopic gene activation requires the sequential activity of qualitatively different TFs. We tested the PFH by expressing the endodermal PF FOXA1 and non-PF HNF4A in K562 lymphoblast cells. While co-expression of FOXA1 and HNF4A activated a burst of endoderm-specific gene expression, we found no evidence for a functional distinction between these two TFs. When expressed independently, both TFs bound and opened inaccessible sites, activated endodermal genes, and ‘pioneered’ for each other, although FOXA1 required fewer copies of its motif for binding. A subset of targets required both TFs, but the predominant mode of action at these targets did not conform to the sequential activity predicted by the PFH. From these results, we hypothesize an alternative to the PFH where ‘pioneer activity’ depends not on categorically different TFs but rather on the affinity of interaction between TF and DNA. eLife Sciences Publications, Ltd 2022-01-05 /pmc/articles/PMC8849321/ /pubmed/34984978 http://dx.doi.org/10.7554/eLife.73358 Text en © 2022, Hansen et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Chromosomes and Gene Expression
Hansen, Jeffrey L
Loell, Kaiser J
Cohen, Barak A
A test of the pioneer factor hypothesis using ectopic liver gene activation
title A test of the pioneer factor hypothesis using ectopic liver gene activation
title_full A test of the pioneer factor hypothesis using ectopic liver gene activation
title_fullStr A test of the pioneer factor hypothesis using ectopic liver gene activation
title_full_unstemmed A test of the pioneer factor hypothesis using ectopic liver gene activation
title_short A test of the pioneer factor hypothesis using ectopic liver gene activation
title_sort test of the pioneer factor hypothesis using ectopic liver gene activation
topic Chromosomes and Gene Expression
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8849321/
https://www.ncbi.nlm.nih.gov/pubmed/34984978
http://dx.doi.org/10.7554/eLife.73358
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