Toward a mechanistic understanding of DNA binding by forkhead transcription factors and its perturbation by pathogenic mutations

Forkhead box (FOX) proteins are an evolutionarily conserved family of transcription factors that play numerous regulatory roles in eukaryotes during developmental and adult life. Dysfunction of FOX proteins has been implicated in a variety of human diseases, including cancer, neurodevelopment disord...

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Autores principales: Dai, Shuyan, Qu, Linzhi, Li, Jun, Chen, Yongheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Critical Reviews and Perspectives
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501956/
https://www.ncbi.nlm.nih.gov/pubmed/34551426
http://dx.doi.org/10.1093/nar/gkab807
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author Dai, Shuyan
Qu, Linzhi
Li, Jun
Chen, Yongheng
author_facet Dai, Shuyan
Qu, Linzhi
Li, Jun
Chen, Yongheng
author_sort Dai, Shuyan
collection PubMed
description Forkhead box (FOX) proteins are an evolutionarily conserved family of transcription factors that play numerous regulatory roles in eukaryotes during developmental and adult life. Dysfunction of FOX proteins has been implicated in a variety of human diseases, including cancer, neurodevelopment disorders and genetic diseases. The FOX family members share a highly conserved DNA-binding domain (DBD), which is essential for DNA recognition, binding and function. Since the first FOX structure was resolved in 1993, >30 FOX structures have been reported to date. It is clear now that the structure and DNA recognition mechanisms vary among FOX members; however, a systematic review on this aspect is lacking. In this manuscript, we present an overview of the mechanisms by which FOX transcription factors bind DNA, including protein structures, DNA binding properties and disease-causing mutations. This review should enable a better understanding of FOX family transcription factors for basic researchers and clinicians.
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spelling pubmed-85019562021-10-12 Toward a mechanistic understanding of DNA binding by forkhead transcription factors and its perturbation by pathogenic mutations Dai, Shuyan Qu, Linzhi Li, Jun Chen, Yongheng Nucleic Acids Res Critical Reviews and Perspectives Forkhead box (FOX) proteins are an evolutionarily conserved family of transcription factors that play numerous regulatory roles in eukaryotes during developmental and adult life. Dysfunction of FOX proteins has been implicated in a variety of human diseases, including cancer, neurodevelopment disorders and genetic diseases. The FOX family members share a highly conserved DNA-binding domain (DBD), which is essential for DNA recognition, binding and function. Since the first FOX structure was resolved in 1993, >30 FOX structures have been reported to date. It is clear now that the structure and DNA recognition mechanisms vary among FOX members; however, a systematic review on this aspect is lacking. In this manuscript, we present an overview of the mechanisms by which FOX transcription factors bind DNA, including protein structures, DNA binding properties and disease-causing mutations. This review should enable a better understanding of FOX family transcription factors for basic researchers and clinicians. Oxford University Press 2021-09-22 /pmc/articles/PMC8501956/ /pubmed/34551426 http://dx.doi.org/10.1093/nar/gkab807 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Critical Reviews and Perspectives
Dai, Shuyan
Qu, Linzhi
Li, Jun
Chen, Yongheng
Toward a mechanistic understanding of DNA binding by forkhead transcription factors and its perturbation by pathogenic mutations
title Toward a mechanistic understanding of DNA binding by forkhead transcription factors and its perturbation by pathogenic mutations
title_full Toward a mechanistic understanding of DNA binding by forkhead transcription factors and its perturbation by pathogenic mutations
title_fullStr Toward a mechanistic understanding of DNA binding by forkhead transcription factors and its perturbation by pathogenic mutations
title_full_unstemmed Toward a mechanistic understanding of DNA binding by forkhead transcription factors and its perturbation by pathogenic mutations
title_short Toward a mechanistic understanding of DNA binding by forkhead transcription factors and its perturbation by pathogenic mutations
title_sort toward a mechanistic understanding of dna binding by forkhead transcription factors and its perturbation by pathogenic mutations
topic Critical Reviews and Perspectives
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501956/
https://www.ncbi.nlm.nih.gov/pubmed/34551426
http://dx.doi.org/10.1093/nar/gkab807
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AT lijun towardamechanisticunderstandingofdnabindingbyforkheadtranscriptionfactorsanditsperturbationbypathogenicmutations
AT chenyongheng towardamechanisticunderstandingofdnabindingbyforkheadtranscriptionfactorsanditsperturbationbypathogenicmutations

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