In vertebrates, the genes encoding the class oftranscription factors calledhomeobox 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.Methylation of this gene may result in the loss of its expression and, since the encoded protein upregulates the tumor suppressorp53, this protein may play an important role intumorigenesis.[7]
HoxA5 is controlled, at least in part, byDNA methylation.[8] HoxA5 has been shown to upregulate the tumor suppressor p53 andAKT1 by downregulation ofPTEN.[9] Suppression of HoxA5 has been shown to attenuatehemangioma growth.[10] HoxA5 has far-reaching effects on gene expression, causing ~300 genes to become upregulated upon its induction in breast cancer cell lines.[11] HoxA5 protein transduction domain overexpression prevents inflammation shown by inhibition ofTNFα-inducible monocyte binding toHUVECs.[12][13]
Comparison of the HoxA5promoter methylation profile across cell types from the least differentiated (human embryonic stem cells) to the most endothelial-like (human umbilical vein endothelial cells, or HUVECs) shows that the HoxA5 promoter is normally heavily methylated in non-differentiated cells and becomes demethylated as cells differentiate down theendothelial lineage.[14] HoxA5 contains aC-Amp Response Elements (CRE) in its promoter.[8] POL2 andCTCF binding are enriched at theCpG-dense HoxA5 promoter in HUVECs, demonstrating transcriptional activity.[14]
HoxA5 is suppressed inacute myeloid leukemia (AML), and theDNMT inhibitordecitabine (5Aza) is used to treat this disease. While HoxA5 is known to be hypermethylated in AML, it has not yet been shown whether decitabine directly targets these genes for demethylation.[15][16]HOXA5 has also been nominated as anoncogene inglioblastoma.[17]
^Lee JY, Park KS, Cho EJ, Joo HK, Lee SK, Lee SD, Park JB, Chang SJ, Jeon BH (Jul 2011). "Human HOXA5 homeodomain enhances protein transduction and its application to vascular inflammation".Biochemical and Biophysical Research Communications.410 (2):312–6.doi:10.1016/j.bbrc.2011.05.139.PMID21664342.
1hom: DETERMINATION OF THE THREE-DIMENSIONAL STRUCTURE OF THE ANTENNAPEDIA HOMEODOMAIN FROM DROSOPHILA IN SOLUTION BY 1H NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY
1san: THE DES(1-6)ANTENNAPEDIA HOMEODOMAIN: COMPARISON OF THE NMR SOLUTION STRUCTURE AND THE DNA BINDING AFFINITY WITH THE INTACT ANTENNAPEDIA HOMEODOMAIN
