HOXA3 explained

Homeobox protein Hox-A3 is a protein that in humans is encoded by the HOXA3 gene.^{[1] [2] [3]}

Function

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.

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). 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. Mutant HoxA3 models show similar phenotypes as those seen in DiGeorge's syndrome, and it is possible that the two are linked.

Regulation

The HOXA3 gene is repressed by the microRNA miR-10a.^[7]

See also

• Homeobox

Further reading

• Apiou F, Flagiello D, Cillo C, Malfoy B, Poupon MF, Dutrillaux B . Fine mapping of human HOX gene clusters . Cytogenetics and Cell Genetics . 73 . 1–2 . 114–5 . 1996 . 8646877 . 10.1159/000134320 .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . September 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Manley NR, Capecchi MR . Hox group 3 paralogs regulate the development and migration of the thymus, thyroid, and parathyroid glands . Developmental Biology . 195 . 1 . 1–15 . March 1998 . 9520319 . 10.1006/dbio.1997.8827 . free .
• Toward a complete human genome sequence . Genome Research . 8 . 11 . 1097–108 . November 1998 . 9847074 . 10.1101/gr.8.11.1097 . free . ((Sanger Centre)), ((Washington University Genome Sequencing Center)) .
• Mulder GB, Manley N, Maggio-Price L . 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 . December 1998 . 9894676 . 10.1002/(SICI)1096-9926(199812)58:6<263::AID-TERA8>3.0.CO;2-A .
• Manzanares M, Nardelli J, Gilardi-Hebenstreit P, Marshall H, Giudicelli F, Martínez-Pastor MT, Krumlauf R, Charnay P . Krox20 and kreisler co-operate in the transcriptional control of segmental expression of Hoxb3 in the developing hindbrain . The EMBO Journal . 21 . 3 . 365–76 . February 2002 . 11823429 . 125344 . 10.1093/emboj/21.3.365 .
• Kosaki K, Kosaki R, Suzuki T, Yoshihashi H, Takahashi T, Sasaki K, Tomita M, McGinnis W, Matsuo N . Complete mutation analysis panel of the 39 human HOX genes . Teratology . 65 . 2 . 50–62 . February 2002 . 11857506 . 10.1002/tera.10009 .
• Kim J, Bhinge AA, Morgan XC, Iyer VR . Mapping DNA-protein interactions in large genomes by sequence tag analysis of genomic enrichment . Nature Methods . 2 . 1 . 47–53 . January 2005 . 15782160 . 10.1038/nmeth726 . 6135437 .
• Wissmüller S, Kosian T, Wolf M, Finzsch M, Wegner M . The high-mobility-group domain of Sox proteins interacts with DNA-binding domains of many transcription factors . Nucleic Acids Research . 34 . 6 . 1735–44 . 2006 . 16582099 . 1421504 . 10.1093/nar/gkl105 .

Notes and References

1. McAlpine PJ, Shows TB . Nomenclature for human homeobox genes . Genomics . 7 . 3 . 460 . July 1990 . 1973146 . 10.1016/0888-7543(90)90186-X .
2. Scott MP . Vertebrate homeobox gene nomenclature . Cell . 71 . 4 . 551–3 . November 1992 . 1358459 . 10.1016/0092-8674(92)90588-4 . 13370372 .
3. Web site: Entrez Gene: HOXA3 homeobox A3.
4. Hunt P, Gulisano M, Cook M, Sham MH, Faiella A, Wilkinson D, Boncinelli E, Krumlauf R . A distinct Hox code for the branchial region of the vertebrate head . Nature . 353 . 6347 . 861–4 . October 1991 . 1682814 . 10.1038/353861a0 . 1991Natur.353..861H . 4312466 .
5. Manley NR, Capecchi MR . The role of Hoxa-3 in mouse thymus and thyroid development . Development . 121 . 7 . 1989–2003 . July 1995 . 10.1242/dev.121.7.1989 . 7635047 .
6. Chojnowski JL, Masuda K, Trau HA, Thomas K, Capecchi M, Manley NR . Multiple roles for HOXA3 in regulating thymus and parathyroid differentiation and morphogenesis in mouse . Development . 141 . 19 . 3697–708 . October 2014 . 25249461 . 10.1242/dev.110833 . 4197593 .
7. Han L, Witmer PD, Casey E, Valle D, Sukumar S . DNA methylation regulates MicroRNA expression . Cancer Biology & Therapy . 6 . 8 . 1284–8 . August 2007 . 17660710 . 10.4161/cbt.6.8.4486 . free .