Gene insulation. Part II: natural strategies in vertebrates.

The way a gene is insulated from its genomic environment in vertebrates is not basically different from what is observed in yeast and Drosophila (preceding article in this issue). If the formation of a looped chromatin domain, whether generated by attachment to the nuclear matrix or not, has become a classic way to confine an enhancer to a specific genomic domain and to coordinate, sequentially or simultaneously, gene expression in a given program, its role has been extended to new networks of genes or regulators within the same gene. A wider definition of the bases of the chromatin loops (nonchromosomal nuclear structures or genomic interacting elements) is also available. However, whereas insulation in Drosophila is due to a variety of proteins, in vertebrates insulators are still practically limited to CTCF (the CCCTC-binding factor), which appears in all cases to be the linchpin of an architecture that structures the assembly of DNA-protein interactions for gene regulation. As in yeast and Drosophila, the economy of means is the rule and the same unexpected diversion of known transcription elements (active or poised RNA polymerases, TFIIIC elements out of tRNA genes, permanent histone replacement) is observed, with variants peculiar to CTCF. Thus, besides structuring DNA looping, CTCF is a barrier to DNA methylation or interferes with all sorts of transcription processes, such as that generating heterochromatin.