In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. Three transcript variants encoding two different isoforms have been found for this gene.[3]
During normal fetal development, HoxA3 is expressed in mesenchymal neural crest cells and endodermal cells found in the third pharyngeal pouch.[4] Expression of HoxA3 in these cells affects the proper formation of the thymus, thyroid, and parathyroid organs.[5][6] While the gene does not seem to affect the proliferation or migration of the pharyngeal neural crest cells, it does appear to trigger cellular differentiation events required to form these organs.[5] Knockout of HoxA3 leads to failure in forming the thymus (athymia) and parathyroid gland (aparthyroidism).[6] Mutant HoxA3 also causes a reduction in thyroid size. While the follicular and parafollicular cells still differentiate, their numbers are reduced and they are not evenly distributed throughout the gland.[5] Mutant HoxA3 models show similar phenotypes as those seen in DiGeorge’s Syndrome, and it is possible that the two are linked.[5]
↑Hunt P, Gulisano M, Cook M, Sham MH, Faiella A, Wilkinson D, Boncinelli E, Krumlauf R (October 1991). "A distinct Hox code for the branchial region of the vertebrate head". Nature. 353 (6347): 861–4. doi:10.1038/353861a0. PMID1682814.
↑ 5.05.15.25.3Manley NR, Capecchi MR (July 1995). "The role of Hoxa-3 in mouse thymus and thyroid development". Development. 121 (7): 1989–2003. PMID7635047.
↑Han L, Witmer PD, Casey E, Valle D, Sukumar S (August 2007). "DNA methylation regulates MicroRNA expression". Cancer Biology & Therapy. 6 (8): 1284–8. doi:10.4161/cbt.6.8.4486. PMID17660710.
Further reading
Apiou F, Flagiello D, Cillo C, Malfoy B, Poupon MF, Dutrillaux B (1996). "Fine mapping of human HOX gene clusters". Cytogenetics and Cell Genetics. 73 (1–2): 114–5. doi:10.1159/000134320. PMID8646877.
Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID8889548.
Manley NR, Capecchi MR (March 1998). "Hox group 3 paralogs regulate the development and migration of the thymus, thyroid, and parathyroid glands". Developmental Biology. 195 (1): 1–15. doi:10.1006/dbio.1997.8827. PMID9520319.
Mulder GB, Manley N, Maggio-Price L (December 1998). "Retinoic acid-induced thymic abnormalities in the mouse are associated with altered pharyngeal morphology, thymocyte maturation defects, and altered expression of Hoxa3 and Pax1". Teratology. 58 (6): 263–75. doi:10.1002/(SICI)1096-9926(199812)58:6<263::AID-TERA8>3.0.CO;2-A. PMID9894676.
Kosaki K, Kosaki R, Suzuki T, Yoshihashi H, Takahashi T, Sasaki K, Tomita M, McGinnis W, Matsuo N (February 2002). "Complete mutation analysis panel of the 39 human HOX genes". Teratology. 65 (2): 50–62. doi:10.1002/tera.10009. PMID11857506.
Kim J, Bhinge AA, Morgan XC, Iyer VR (January 2005). "Mapping DNA-protein interactions in large genomes by sequence tag analysis of genomic enrichment". Nature Methods. 2 (1): 47–53. doi:10.1038/nmeth726. PMID15782160.