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

Shuyan Dai; Linzhi Qu; Jun Li; Yongheng Chen

doi:10.1093/nar/gkab807

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

Nucleic Acids Res. 2021 Oct 11;49(18):10235-10249. doi: 10.1093/nar/gkab807.

Authors

Shuyan Dai¹, Linzhi Qu¹, Jun Li¹, Yongheng Chen¹

Affiliation

¹ Department of Oncology, NHC Key Laboratory of Cancer Proteomics, Laboratory of Structural Biology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

DNA / metabolism*
Forkhead Transcription Factors / metabolism*
Humans
Molecular Structure
Neurodevelopmental Disorders / metabolism*
Protein Binding

Substances

Forkhead Transcription Factors
DNA