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Regulation of gene expression by FOXA1

Chenguang Li,D. Geng,Wei Zhao,Yue Ma,Wei Xu

Published 2025 in Oncology and Translational Medicine

ABSTRACT

The forkhead box (FOX) family represents a class of transcription factors characterized by a distinctive winged helical structure. Forkhead box A1 (FOXA1), a member of the forkhead box A (FOXA) subfamily within the FOX gene family, was the first forkhead protein identified in mammals. It serves as a pivotal transcription factor in tissue-specific differentiation and functions. Upon activation, owing to its unique structural domains, FOXA1 can interact with nucleosomes to open chromatin, thereby facilitating the recruitment of other transcription factors. These factors may act independently or synergistically with recruited transcription factors to regulate gene expression. Consequently, FOXA1 and other FOXA subfamily members with similar functions are referred to as “pioneer factors.” In recent years, studies on FOXA1 have advanced our understanding of its crucial role in gene regulation and involvement in disease processes. However, owing to their tissue-specific effects and varying biological behaviors in different environmental contexts, the underlying mechanisms remain elusive. We used the PubMed database to better understand the complex mechanisms of FOXA1. By using keywords such as “FOXA1” and “transcription factor,” an extensive literature was retrieved, and many of the most relevant publications were screened. The selected studies were then thoroughly synthesized and summarized. This review synthesizes recent findings on FOXA1, encompassing its structural characteristics, domain functions, roles in embryonic development and the maintenance of adult organ morphology and function, interactions with histone posttranslational modifications in gene regulation, and the influence of its posttranslational modifications on gene expression. We also explore the involvement of FOXA1 in various diseases. By elucidating the biological mechanisms and disease-related roles of FOXA1, this review aims to provide insights for future research on its complex mechanisms and potential therapeutic targets.

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