7vox

Structural highlights

Function

FOXA1_HUMAN Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. Is thought to act as a 'pioneer' factor opening the compacted chromatin for other proteins through interactions with nucleosomal core histones and thereby replacing linker histones at target enhancer and/or promoter sites. Binds DNA with the consensus sequence 5'-[AC]A[AT]T[AG]TT[GT][AG][CT]T[CT]-3' (By similarity). Proposed to play a role in translating the epigenetic signatures into cell type-specific enhancer-driven transcriptional programs. Its differential recruitment to chromatin is dependent on distribution of histone H3 methylated at 'Lys-5' (H3K4me2) in estrogen-regulated genes. Involved in the development of multiple endoderm-derived organ systems such as liver, pancreas, lung and prostate; FOXA1 and FOXA2 seem to have at least in part redundant roles (By similarity). Modulates the transcriptional activity of nuclear hormone receptors. Is involved in ESR1-mediated transcription; required for ESR1 binding to the NKX2-1 promoter in breast cancer cells; binds to the RPRM promoter and is required for the estrogen-induced repression of RPRM. Involved in regulation of apoptosis by inhibiting the expression of BCL2. Involved in cell cycle regulation by activating expression of CDKN1B, alone or in conjunction with BRCA1. Originally described as a transcription activator for a number of liver genes such as AFP, albumin, tyrosine aminotransferase, PEPCK, etc. Interacts with the cis-acting regulatory regions of these genes. Involved in glucose homeostasis.^{[1] [2] [3] [4] [5]}

References

1. ↑ Laganiere J, Deblois G, Lefebvre C, Bataille AR, Robert F, Giguere V. From the Cover: Location analysis of estrogen receptor alpha target promoters reveals that FOXA1 defines a domain of the estrogen response. Proc Natl Acad Sci U S A. 2005 Aug 16;102(33):11651-6. doi:, 10.1073/pnas.0505575102. Epub 2005 Aug 8. PMID:16087863 doi:http://dx.doi.org/10.1073/pnas.0505575102
2. ↑ Williamson EA, Wolf I, O'Kelly J, Bose S, Tanosaki S, Koeffler HP. BRCA1 and FOXA1 proteins coregulate the expression of the cell cycle-dependent kinase inhibitor p27(Kip1). Oncogene. 2006 Mar 2;25(9):1391-9. doi: 10.1038/sj.onc.1209170. PMID:16331276 doi:http://dx.doi.org/10.1038/sj.onc.1209170
3. ↑ Lupien M, Eeckhoute J, Meyer CA, Wang Q, Zhang Y, Li W, Carroll JS, Liu XS, Brown M. FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription. Cell. 2008 Mar 21;132(6):958-70. doi: 10.1016/j.cell.2008.01.018. PMID:18358809 doi:http://dx.doi.org/10.1016/j.cell.2008.01.018
4. ↑ Song L, Wei X, Zhang B, Luo X, Liu J, Feng Y, Xiao X. Role of Foxa1 in regulation of bcl2 expression during oxidative-stress-induced apoptosis in A549 type II pneumocytes. Cell Stress Chaperones. 2009 Jul;14(4):417-25. doi: 10.1007/s12192-008-0095-4., Epub 2009 Jan 7. PMID:19127412 doi:http://dx.doi.org/10.1007/s12192-008-0095-4
5. ↑ Malik S, Jiang S, Garee JP, Verdin E, Lee AV, O'Malley BW, Zhang M, Belaguli NS, Oesterreich S. Histone deacetylase 7 and FoxA1 in estrogen-mediated repression of RPRM. Mol Cell Biol. 2010 Jan;30(2):399-412. doi: 10.1128/MCB.00907-09. Epub 2009 Nov, 16. PMID:19917725 doi:http://dx.doi.org/10.1128/MCB.00907-09
6. ↑ Choi Y, Luo Y, Lee S, Jin H, Yoon HJ, Hahn Y, Bae J, Lee HH. FOXL2 and FOXA1 cooperatively assemble on the TP53 promoter in alternative dimer configurations. Nucleic Acids Res. 2022 Aug 26;50(15):8929-8946. doi: 10.1093/nar/gkac673. PMID:35920317 doi:http://dx.doi.org/10.1093/nar/gkac673