HOX Genes and HOX Codes

The HOX genes (1,2) are homeobox genes but not all homeobox genes are HOX genes (3). HOX genes encode transcription factors (homeoproteins) which are activators and repressor of expression during vertebrate development (4).  The HOX genes are located in clusters (nested) (5-8).  It is apparent that increased metazoan complexity is a consequence of more complex gene regulation, in particular cis factors, and not an increased number of genes (9).  The expression of HOX genes (39 in human) is mediated or controlled by the Hox-code (10- 13)  Knowledge of the HOX code of donor cells is important in tissue transplantation (14) and other areas of regenerative medicine where HOX expression patterns are determined by  reverse transcription-polymerase chain reaction (15) RNA-seq has also been used to measure HOX gene expression (16).  Hox gene expression is important in cancer research (17,18).  HOTAIR is a long noncoding RNA hat regulates HOX gene expression (19).


1.  Morgan, S., HOX genes: a continuation of embryonic patterning? Trends in Genetics 22, 67-69, 2006.
2.  Gehring, W.J., Kloter, U., and Suga, H., Evolution of the Hox  gene complex from an evolutionary ground state, Curr.Topics Develop.Biol. 88, 35-61, 2009.
3.  Deutsch, J.S., Homeosis and beyond. What is the function of Hox genes?, in Hox Genes studies from the 20th to the 21st Century, ed. J.S. Deutsch, Landes Bioscience/Springer Science + Business, New York, New York, USA, 2010.
4.  Merabet, S., Sambrani, N., Pradel, J., and Graba, Y., Regulation of Hox activity: Insights from protein motifs, in Hox Genes: Studies from the 20th to the 21st Century, ed. J.S. Deutsch, Chapter 1, pps. 3-16, Landes Bioscience and Springer Science+Business, New York, New York, USA,2010)
5.  Hoegg, S. and Meyer, A., HOX clusters as models for vertebrate genome evolution, Trends in Genetics 21, 421-424, 2005;.
6. Duboule, D., The rise and fall of Hox gene clusters, Development  134, 2549-2560, 2007.
7.  Nolte, C., Jinks, T., Wang, X., Martinez Pastor, M.T., and Krumlauf, R., Shadow enhancers flanking  the HoxB cluseter direct dynamic Hox expression in early heart and endoderm development, Dev.Biol. 383, 158-173, 2013.
8. Parker, H.J., Pushel, I., and Krumlauf, R., Coupling the roles of Hox genes to regulatory patterning cranial neural crest, Dev.BIol., in press (doi: 10.1016/j.ydbio.2018.03.016), 2018.
9. (Erwin, D.H. The developmental origins of animal bodyplans, in Neoproterozoic Geobilogy and Paleobiology, ed. S. Xiao and A.J Kaufman, Chapter 6, pps. 159-197, Springer, Dordrecht, Netherlands, 2006)
10.  Lewis, S.A., A gene complex controlling segmentation in Drosophila, Nature 276, 565-570, 1978. 
11.  Hunt, P. and Krumlaw, R., Deciphering the Hox code: Clues to patterning branchial regions of head, Cell 66, 1075-1078, 1991.
12.  Sekimoto, T., Yoshinobu, K., Yoshida, M., et al., Region-specific expression of murine Hox genes implies the HOX code-mediated patterning of the digestive tract, Genes to Cells 3, 51-64, 1998.
13. Wellik, D.M. Hos genes and the vertebrate skeleton, Curr.Top.Develop.Biol. 88, 257-273, 2009.
14. Foissac, R., Villageois, P., Chignon-Sicard, B., et al, Homeotic and embryonic gene expression in breast adipose tissue and in adipose tissues used as donor sites in plastic surgery, Plast.Reconstr.Surg. 139, 685e-692e, 2017.
15. Liedtke, S., Sacchetti, B., Laitinen, A., et al., Low oxygen tension reveals distinct HOX codes in human cord blood-derived stromal cells associated with specific endochondral ossification capacities in vitro and in vivo, J.Tissue Eng.Regen.Med. 11, 2725-2736, 2017.
16. Knight, J.M., Kim, E., Ivanov, I., et al., Comprehensive site-specific whole genome profiling of stromal and epithelial colonic gene signatures in human sigmoid colon and rectal tissue, Physiol.Genomics 48, 651-659, 2016.
17.  Bhatlekar, S., Fields, J.Z., and Boman, B.M., HOX genes and their role in the development of haman cancers, J.Mol.Med.(Berl.) 92, 811-823, 2014.
18.  Xiang, S., Zou, P., Tang, Q., et al., HOTAIR-mediated reciprocal regulation of EZH2 and DNMT1 contribute to polyphyllin I-inhibited growth of castration -resistant prostate cancer cells in vitro and in vivo, Biochim.Biophys.Acta 1862, 589-599, 2018.
19.  Woo, C.J. and Kingston, R.E., HOTAIR lifts noncoding RNAs to new levels, Cell 129, 1257-1259, 2007.