Epigenetic control of Hox genes during neurogenesis, development, and disease

The process of mammalian development is established through multiple complex molecular pathways acting in harmony at the genomic, proteomic, and epigenomic levels. The outcome is profoundly influenced by the role of epigenetics through transcriptional regulation of key developmental genes. Epigenetics refer to changes in gene expression that are inherited through mechanisms other than the underlying DNA sequence, which control cellular morphology and identity. It is currently well accepted that epigenetics play central roles in regulating mammalian development and cellular differentiation by dictating cell fate decisions via regulation of specific genes. Among these genes are the Hox family members, which are master regulators of embryonic development and stem cell differentiation and their mis-regulation leads to human disease and cancer. The Hox gene discovery led to the establishment of a fundamental role for basic genetics in development. Hox genes encode for highly conserved transcription factors from flies to humans that organize the anterior-posterior body axis during embryogenesis. Hox gene expression during development is tightly regulated in a spatiotemporal manner, partly by chromatin structure and epigenetic modifications. Here, we review the impact of different epigenetic mechanisms in development and stem cell differentiation with a clear focus on the regulation of Hox genes.