This protein belongs to the basic helix-loop-helix (BHLH) family of transcription factors. It activates E-box dependent transcription along with E47.[2] ATOH1 is required for the formation of both neural and non-neural cell types. Using genetic deletion in mice, Atoh1 has been shown to be essential for formation of cerebellar granule neurons, inner ear hair cells, spinal cord interneurons, Merkel cells of the skin, and intestinal secretory cells (goblet, enteroendocrine, and Paneth cells). ATOH1 is a mammalian homolog of the Drosophila melanogaster gene atonal. ATOH1 is considered part of the Notch signaling pathway.
In 2009, ATOH1 was identified as a "cancer switch-off" gene. [2]
References
↑Ben-Arie N, McCall AE, Berkman S, Eichele G, Bellen HJ, Zoghbi HY (Sep 1996). "Evolutionary conservation of sequence and expression of the bHLH protein Atonal suggests a conserved role in neurogenesis". Human Molecular Genetics. 5 (9): 1207–16. doi:10.1093/hmg/5.9.1207. PMID8872459.
Helms AW, Johnson JE (Mar 1998). "Progenitors of dorsal commissural interneurons are defined by MATH1 expression". Development. 125 (5): 919–28. PMID9449674.
Leonard JH, Cook AL, Van Gele M, Boyle GM, Inglis KJ, Speleman F, Sturm RA (Sep 2002). "Proneural and proneuroendocrine transcription factor expression in cutaneous mechanoreceptor (Merkel) cells and Merkel cell carcinoma". International Journal of Cancer. 101 (2): 103–10. doi:10.1002/ijc.10554. PMID12209986.
Gazit R, Krizhanovsky V, Ben-Arie N (Feb 2004). "Math1 controls cerebellar granule cell differentiation by regulating multiple components of the Notch signaling pathway". Development. 131 (4): 903–13. doi:10.1242/dev.00982. PMID14757642.
Leow CC, Polakis P, Gao WQ (Nov 2005). "A role for Hath1, a bHLH transcription factor, in colon adenocarcinoma". Annals of the New York Academy of Sciences. 1059: 174–83. doi:10.1196/annals.1339.048. PMID16382053.
Sekine A, Akiyama Y, Yanagihara K, Yuasa Y (Jun 2006). "Hath1 up-regulates gastric mucin gene expression in gastric cells". Biochemical and Biophysical Research Communications. 344 (4): 1166–71. doi:10.1016/j.bbrc.2006.03.238. PMID16647036.
Mutoh H, Sakamoto H, Hayakawa H, Arao Y, Satoh K, Nokubi M, Sugano K (Jul 2006). "The intestine-specific homeobox gene Cdx2 induces expression of the basic helix-loop-helix transcription factor Math1". Differentiation; Research in Biological Diversity. 74 (6): 313–21. doi:10.1111/j.1432-0436.2006.00074.x. PMID16831200.
Park ET, Oh HK, Gum JR, Crawley SC, Kakar S, Engel J, Leow CC, Gao WQ, Kim YS (Sep 2006). "HATH1 expression in mucinous cancers of the colorectum and related lesions". Clinical Cancer Research. 12 (18): 5403–10. doi:10.1158/1078-0432.CCR-06-0573. PMID17000673.
Tsuchiya K, Nakamura T, Okamoto R, Kanai T, Watanabe M (Jan 2007). "Reciprocal targeting of Hath1 and beta-catenin by Wnt glycogen synthase kinase 3beta in human colon cancer". Gastroenterology. 132 (1): 208–20. doi:10.1053/j.gastro.2006.10.031. PMID17241872.
Du X, Jensen P, Goldowitz D, Hamre KM (May 2007). "Wild-type cells rescue genotypically Math1-null hair cells in the inner ears of chimeric mice". Developmental Biology. 305 (2): 430–8. doi:10.1016/j.ydbio.2007.02.028. PMID17397818.
Westerman BA, Breuer RH, Poutsma A, Chhatta A, Noorduyn LA, Koolen MG, Postmus PE, Blankenstein MA, Oudejans CB (2007). "Basic helix-loop-helix transcription factor profiling of lung tumors shows aberrant expression of the proneural gene atonal homolog 1 (ATOH1, HATH1, MATH1) in neuroendocrine tumors". The International Journal of Biological Markers. 22 (2): 114–23. PMID17549667.
Scheffer D, Sage C, Corey DP, Pingault V (Oct 2007). "Gene expression profiling identifies Hes6 as a transcriptional target of ATOH1 in cochlear hair cells". FEBS Letters. 581 (24): 4651–6. doi:10.1016/j.febslet.2007.08.059. PMID17826772.
Shroyer NF, Helmrath MA, Wang VY, Antalffy B, Henning SJ, Zoghbi HY (Jun 2007). "Intestine-specific ablation of mouse atonal homolog 1 (Math1) reveals a role in cellular homeostasis". Gastroenterology. 132 (7): 2478–88. doi:10.1053/j.gastro.2007.03.047. PMID17570220.