The Enigmatic HOX Genes: Can We Crack Their Code?

Homeobox genes (HOX) are a large family of transcription factors that direct the formation of many body structures during early embryonic development. There are 39 genes in the subgroup of homeobox genes that constitute the human HOX gene family. Correct embryonic development of flies and vertebrates is, in part, mediated by the unique and highly regulated expression pattern of the HOX genes. Disruptions in these fine-tuned regulatory mechanisms can lead to developmental problems and to human diseases such as cancer. Unfortunately, the molecular mechanisms of action of the HOX family of transcription factors are severely under-studied, likely due to idiosyncratic details of their structure, expression, and function. We suggest that a concerted and collaborative effort to identify interacting protein partners, produce genome-wide binding profiles, and develop HOX network inhibitors in a variety of human cell types will lead to a deeper understanding of human development and disease. Within, we review the technological challenges and possible approaches needed to achieve this goal.