FOXA2
Description
The FOXA2 (forkhead box A2) is a protein-coding gene located on chromosome 20.
FOXA2, also known as hepatocyte nuclear factor 3-beta (HNF-3B), is a transcription factor that plays an important role during development, in mature tissues and, when dysregulated or mutated, also in cancer. FOXA2 belongs to a subfamily of the Forkhead box (FOX) transcription factors, the other members being FOXA1 and FOXA3. This subfamily of mammalian FOX proteins was first identified because of their ability to bind DNA in rat liver nuclear extracts. The proteins were therefore originally named hepatocyte nuclear factor 3 alpha, beta and gamma. These transcription factors contain a forkhead domain (also known as the winged-helix domain) flanked by sequences necessary for nuclear localization Their N- and C-termini are also conserved and serve as transactivation domains. FOXA transcription factors have “pioneering” property, i.e. they can directly bind to condensed chromatin. This feature has been observed both in vitro and in vivo, where FOXA transcription factors can bind nucleosome-bound target DNA sequences. The pioneering property is conferred by the factors’ highly conserved DNA-binding domain, which is structurally similar to the linker histones H1 and H5 This feature enables FOXA2 to access closed chromatin and displace linker histones. In this way, FOXA2 promotes local chromatin opening, permits the recruitment of alternative histones and facilitates the subsequent binding of other transcription factors.
FOXA2 is a transcription factor that plays a crucial role in embryonic development, establishing tissue-specific gene expression, and regulating gene expression in mature tissues. It acts as a 'pioneer' factor, opening up tightly packed chromatin to allow access for other proteins. This is achieved through interactions with nucleosomal core histones, effectively replacing linker histones at target enhancer and/or promoter sites. It binds to DNA with a specific consensus sequence: 5'-[AC]A[AT]T[AG]TT[GT][AG][CT]T[CT]-3'. FOXA2 is essential for notochord formation during embryonic development. It is also involved in the development of various endoderm-derived organs, including the liver, pancreas, and lungs, with some redundancy observed between FOXA1 and FOXA2. Originally identified as a transcription activator for several liver genes, including AFP, albumin, tyrosine aminotransferase, and PEPCK, it interacts with their cis-acting regulatory regions. FOXA2 contributes to glucose homeostasis by regulating genes crucial for glucose sensing in pancreatic beta-cells. It is also involved in regulating fat metabolism. It binds to the fibrinogen beta promoter and participates in IL6-induced fibrinogen beta transcriptional activation.
FOXA2 is also known as HNF-3-beta, HNF3B, TCF3B.
