FOXA1 (forkhead box A1)

Alias (NCBI)	HNF3A
	MGC33105
	TCF3A
HGNC (Hugo)	FOXA1
HGNC Previous name	HNF3A
HGNC Previous name	hepatocyte nuclear factor 3, alpha
LocusID (NCBI)	3169
Atlas_Id	44403
Location	14q21.1  [Link to chromosome band 14q21]
Location_base_pair	Starts at 37589552 and ends at 37595249 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping FOXA1.png]
	FOXA1 is located on chromosome 14q21.1 and the transcribed region including an intron spans only 5300 bases. This protein binds to chromatinized DNA and, therefore, described as a "pioneer factor".

Description	The transcribed region of FOXA1 extends only to 5400 bases and contains two exons and one intron. This gene is amplified in breast, esophageal, lung, and thyroid carcinomas. No deletions or chromosomal translocations have been reported. MIPOL1 and C14orf25 are the two adjoining genes. MIPOL1 has been described as a tumor suppressor gene in nasopharyngeal carcinoma, whereas the function of C14orf25 is unknown.
Transcription	FOXA1 is expressed predominantly in liver and is highly responsive to hormonal manipulation. Insulin suppresses its expression in embryonic stem cells as well as in breast cancer cells, whereas retinoic acid, estrogen, androgen, and heregulin induce its expression. The developmental transcription factors Oct-4 and SOX4 repress FOXA1 expression, whereas SOX17 and GATA-3 increase its expression. No splice variants have been reported. 542 base long promoter/enhancer is sufficient for liver-specific expression. This region binds to transcription factors TTF1 and NF-1. By binding to its own enhancer/promoter, FOXA1 autoregulates its expression. Peroxisome Proliferator Activated Receptor gamma also upregulates FOXA1 expression, although region of the promoter/enhancer involved in this upregulation is yet to be characterized.

Description	FOXA1 is a 473 amino acid long transcription factor that binds to the consensus sequence A(A/T)TRTT(G/T)RYTY using the central region of the protein. Crystallography showed DNA binding domain in a winged helix-loop-helix configuration. Both N-terminus and C-terminus have transactivation domains. In silico analysis revealed 11 putative acetylation sites; acetylation sites in the DNA binding domain inhibit interaction with chromatin. The N-terminus has a putative caseine kinase 1 phosphorylation site.
Expression	FOXA1 was originally identified as a transcription factor that regulates gene expression in endoderm-derived tissues such as liver and lungs. Subsequent studies showed expression in pancreas, breast, prostate, bladder, intestine, and seminal vesicle. During embryogenesis, expression is seen in tissues derived from both foregut and hindgut endoderm (liver, lung, pancreas, stomach, intestine, prostate, and bladder). Organs derived from ectoderm (forebrain, floor plate, olfactory epithelium) and mesoderm (kidney, vagina, uterus, seminal and coagulating glands) also show expression. FOXA1 along with FOXA2 is required for normal bile duct development as deletion of FOXA1/2 in embryonic liver leads to hyperplasia of the billiary tree. Absence of FOXA1 in mammary gland leads to impaired ductal morphogenesis and reduction in the number of estrogen receptor-positive luminal epithelial cells.
Localisation	FOXA1 is localized predominantly in the nucleus. transforming growth factor beta 1 treatment results in cytoplasmic localization of the protein, which may be dependent on protein kinase C.
Function	FOXA1 binds to chromatinized DNA and opens the chromatin to allow binding of additional transcription factors. Specific histone modification such as histone H3 lysine 4 methylation guides recruitment of other factors. FOXA1 facilitates the recruitment of nuclear receptors including estrogen receptor, androgen receptor and glucocorticoid receptor. FOXA1 binding leads to both activation or repression of genes. These gene-specific effects involve interaction with or recruitment of other transcription factors such as SRC-3, USF2, TLE3, COUP-TFII, SHP, SMAD3, and HDAC7.
Homology	FOXA1 belongs to the 40-member FOX family of transcription factors. FOXA1, FOXA2, and FOXA3 form a subfamily and share a 110 amino acid long DNA binding domain with only 7 amino acid difference.

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