Complexity of transcriptional control in neuropeptide gene expression; enkephalin gene regulation during neurodevelopment.

The gene for enkephalin is expressed only in specific subsets of neurons in the mammalian central nervous system (CNS), whereas the large majority of neurons do not express the gene. This restricted expression is the result of a developmental process during which some of the multipotent neural progenitors express the gene for enkephalin and thereby become enkephalinergic neurons. The regulation of this process is not well understood. We have used a novel approach to identify DNA-protein interactions that regulate the developmental expression of the gene for enkephalin. We have identified four novel DNA regulatory sites and their binding proteins that are expressed in the developing mammalian CNS. These protein-DNA interactions regulate DNA and nuclear structures through DNA bending, DNA sliding, chromatin remodelling and far-distant DNA interactions. The concerted and co-ordinated interactions of these four DNA elements and their binding proteins contribute to the guiding of multipotent neural progenitors into enkephalinergic neurons. The provided examples suggest an important role for architectural transcriptional regulation during CNS development.