HOXs

Definition: The Hox genes (HOXs ) encode a family of transcription factors that determine the identity of cells and tissues in the developing embryo. Their intricate pattern of embryonic expression continues into adulthood, where their original embryonic role is modified to meet specific regional needs, especially in tissues that undergo frequent renewal. Hox expression can determine the identity of malignant cells in some tumour types.

In vertebrates, the genes encoding the class of transcription factors called homeobox genes (HOXs ) 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.

Hox proteins regulate specific sets of target genes to give rise to morphological distinctions along the anterior-posterior body axis of metazoans.

Though they have high developmental specificity, Hox proteins have low DNA binding specificity, so how they select the appropriate target genes has remained enigmatic.

HOXs cofactors

Cofactors provide additional specificity, but a comprehensive model of Hox control of gene expression has not emerged. There is now evidence that a global network of zinc finger transcription factors contributes to patterning of the Drosophila embryo.

These zinc finger proteins appear to establish fields in which certain Hox proteins can function. Though the nature of these fields is uncertain at this time, it is possible that these zinc finger proteins are Hox cofactors, providing additional specificity during Hox target-gene selection.

Furthermore, these zinc finger proteins are conserved, as are aspects of their anterior-posterior expression, suggesting that their roles might be conserved.

Members

Hox A cluster at 7p15-p14.2 (HOXAs )

 HOXA1 (MIM.142955)
 HOXA2 (MIM.604685)
 HOXA3 (MIM.142954)
 HOXA4 (MIM.142953)
 HOXA5 (MIM.142952)
 HOXA6 (MIM.142951)
 HOXA7 (MIM.142950)
 HOXA8
 HOXA9 (MIM.142956)
 HOXA10 (MIM.142957)
 HOXA11 (MIM.142958)
 HOXA13 (MIM.142959)

Hox B cluster at 17q21-q22 (HOXBs )

 HOXB1 (MIM.142968)
 HOXB2 (MIM.142967)
 HOXB3 (MIM.142966)
 HOXB4 (MIM.142965)
 HOXB6 (MIM.142961)
 HOXB7 (MIM.142962)
 HOXB8 (MIM.142963)
 HOXB9 (MIM.142964)
 HOXB13 (MIM.604607)

Hox C cluster at 12q13 - HOXCs

 HOXC4 (MIM.142974)
 HOXC6 (MIM.142972)
 HOXC8 (MIM.142970)
 HOXC9 (MIM.142971)
 HOXC10 (MIM.605560)
 HOXC11 (MIM.605559)
 HOXC12
 HOXC13 (MIM.142976)

Hox D cluster at 2q31-q32 (HOXDs )

 HOXD1 (MIM.142987)
 HOXD3 (MIM.142980)
 HOXD4 (MIM.142981)
 HOXD8 (MIM.142985)
 HOXD9 (MIM.142982)
 HOXD10 (MIM.142984)
 HOXD11 (MIM.142986)
 HOXD12 (MIM.142988)
 HOXD13 (MIM.142989)

Pathology

 HOXA9 (MIM.142956) - fused in the HOXA9-MSI2 Fusion Gene by t(7;17)(p15;q23) in chronic myeloid leukemia

 HOX11 (MIM.186770) - translocated at TCRD at 14q11 (MIM.186810) or TCRB at 7q35 (MIM.186930) by t(10;14)(q24;q11) or t(7;10)(q35;q24) in 7% of childhood T-cell acute leukemia

 HOXC13 (MIM.142976) - fused in the HOXC13-NUP98 (MIM.601021) by t(11;12)(p15;q13) in acute myeloid leukemia

 HOXD11 (MIM.142986) - fused in the HOXD11-NUP98 fusion gene by t(2;11)(q31;p15) in acute myeloid leukemia

 HOXD13 (MIM.142989) - fused in the HOXD13-NUP98 fusion gene in acute myeloid leukemia - mutations in synpolydactyly (MIM.186000) with or without foot anomaly, brachydactyly types D (MIM.113200) and E (MIM.113300) (12649808)

 HOXA11 (MIM.142958) germline mutations in radioulnar synostosis with amegakaryocytic thrombocytopenia (MIM.605432)

References

 Morgan R. Hox genes: a continuation of embryonic patterning? Trends Genet. 2006 Feb;22(2):67-9. PMID: 16325300

 Mahaffey JW. Assisting Hox proteins in controlling body form: are there new lessons from flies (and mammals)? Curr Opin Genet Dev. 2005 Aug;15(4):422-9. PMID: 15979870

 Pearson JC, Lemons D, McGinnis W. Modulating Hox gene functions during animal body patterning. Nat Rev Genet. 2005 Dec;6(12):893-904. PMID: 16341070

 Garcia-Fernandez J. The genesis and evolution of homeobox gene clusters. Nat Rev Genet. 2005 Dec;6(12):881-92. PMID: 16341069

 Hoegg S, Meyer A. Hox clusters as models for vertebrate genome evolution. Trends Genet. 2005 Aug;21(8):421-4. PMID: 15967537

 Merabet S, Pradel J, Graba Y. Getting a molecular grasp on Hox contextual activity. Trends Genet. 2005 Sep;21(9):477-80. PMID: 16023254

 Grier DG, Thompson A, Kwasniewska A, McGonigle GJ, Halliday HL, Lappin TR. The pathophysiology of HOX genes and their role in cancer. J Pathol. 2005 Jan;205(2):154-71. PMID: 15643670

 Abate-Shen C. Deregulated homeobox gene expression in cancer: cause or consequence? Nat Rev Cancer. 2002 Oct;2(10):777-85. PMID: 12360280

 Goodman FR. Limb malformations and the human HOX genes. Am J Med Genet. 2002 Oct 15;112(3):256-65. PMID: 12357469

 Goodman FR, Scambler PJ. Human HOX gene mutations. Clin Genet. 2001 Jan;59(1):1-11. PMID: 11206481

 Innis JW. Role of HOX genes in human development. Curr Opin Pediatr. 1997 Dec;9(6):617-22. PMID: 9425595