FOXA1

Official Full Name

forkhead box A1

Organism

Homo sapiens

GeneID

3169

Background

This gene encodes a member of the forkhead class of DNA-binding proteins. These hepatocyte nuclear factors are transcriptional activators for liver-specific transcripts such as albumin and transthyretin, and they also interact with chromatin. Similar family members in mice have roles in the regulation of metabolism and in the differentiation of the pancreas and liver. [provided by RefSeq, Jul 2008]

Synonyms

HNF3A; TCF3A;

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Detailed Information

The FOXA1 gene, located on human chromosome 14q21.1, belongs to the forkhead box (FOX) transcription factor family and encodes a pioneer DNA-binding protein essential for tissue-specific gene regulation. FOXA1 protein contains a highly conserved forkhead domain that recognizes a specific consensus DNA sequence: 5'-[AC]A[AT]T[AG]TT[GT][AG][CT]T[CT]-3'. Originally identified for its critical role in liver-specific transcription, it was classified as hepatocyte nuclear factor 3α (HNF3α) and directly activates genes such as albumin, alpha-fetoprotein, and transthyretin. Unique among transcription factors, FOXA1 possesses pioneer activity, allowing it to bind compacted, repressed chromatin and locally remodel nucleosomes, even displacing linker histones, thereby opening chromatin for recruitment of other transcription factors, coactivators, and RNA polymerase II, establishing transcriptional programs for tissue-specific gene expression.

Biological Significance

FOXA1 plays critical roles in embryonic development, cell differentiation, and metabolic homeostasis. During early embryogenesis, it is essential for the development of endoderm-derived organs, including liver, pancreas, lung, and prostate. FOXA1 functions partially redundantly with FOXA2, together directing organ-specific cell fate decisions and functional specialization. Its pioneer activity enables it to translate epigenetic marks into enhancer-driven, cell type-specific transcriptional programs. For instance, in the estrogen receptor (ER) signaling pathway, FOXA1 binding to chromatin precedes ER recruitment, reshaping local chromatin and guiding ER to its target regulatory elements, thereby controlling downstream gene transcription.

Figure 1. FOXA1/ER signalling in breast cancer. (Bernardo GM, et al., 2012)

Figure 2. FOXA1/AR signalling in prostate cancer. (Bernardo GM, et al., 2012)

In differentiated tissues, FOXA1 regulates cell cycle progression (e.g., activating CDKN1B), apoptosis (e.g., repressing BCL2), and metabolic gene expression, including genes involved in glucose homeostasis. Its most clinically relevant role, however, is in hormone-dependent cancers, particularly breast and prostate cancer. In prostate cancer, FOXA1 is crucial for androgen receptor (AR) signaling, assisting AR in binding target loci. Mutations or dysregulation of FOXA1 can drive tumorigenesis, promoting proliferation, invasion, and progression to castration-resistant prostate cancer. In breast cancer, FOXA1 interacts with ER to influence epithelial cell fate and tumor subtype identity, with expression levels closely associated with molecular subtypes and clinical prognosis.

Clinical Relevance

FOXA1 serves as a biomarker and potential therapeutic target in multiple malignancies. In breast and prostate cancer, FOXA1 expression, subcellular localization, and mutation status are critical for tumor classification, prognostic assessment, and therapeutic decision-making. In breast cancer, FOXA1 expression correlates with luminal A and B subtypes, which are often sensitive to endocrine therapy, making FOXA1 a predictive marker for tamoxifen or aromatase inhibitor response. However, high FOXA1 expression may also associate with more aggressive features, requiring integrated interpretation with other molecular markers.

In prostate cancer, mutations in the forkhead domain alter AR binding profiles, driving aberrant activation of oncogenic programs and contributing to tumor progression and therapy resistance. Directly targeting transcription factors is technically challenging due to their lack of conventional active sites. Nevertheless, indirect interventions targeting FOXA1 function or downstream pathways are emerging. Potential strategies include developing small molecules that disrupt FOXA1–DNA interactions or its functional interactions with histone modifiers and nuclear receptors. Understanding how FOXA1 integrates epigenetic signals and transcription factor networks in tumorigenesis can also reveal synthetic lethal partners, offering new avenues for precision oncology combination therapies.

Overall, FOXA1 represents a key molecular link between developmental biology and oncology, with clinical translation potential in both diagnosis and targeted therapy of hormone-dependent cancers.

References

Robinson JL, Holmes KA, Carroll JS. FOXA1 mutations in hormone-dependent cancers. Trends Cancer. 2013;9(5):369–382.
Iwafuchi-Doi M, Zaret KS. Pioneer transcription factors in cell reprogramming. Genes Dev. 2014;28(24):2679–2692.
Sahu B, Laakso M, Pihlajamaa P, et al. FoxA1 specifies unique androgen and glucocorticoid receptor binding events in prostate cancer cells. Cancer Res. 2013;73(5):1570–1580.
Bernardo GM, Keri RA. FOXA1: a transcription factor with parallel functions in development and cancer. Biosci Rep. 2012 Apr 1;32(2):113-30.

Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry