Link Between Double-Strand DNA Break Hotspots and Transcription Regulation: Forum Domains - 50-250 kb Chromosome Regions Containing Coordinately Expressed Genes.

The data on forum domains formed by DNA double-strand break (DSB) hotspots are reviewed including forum domain identification by pulsed-field gel electrophoresis, whole genome mapping of these domains using deep sequencing strategies, analysis of gene expression in forum domains, and binding of nuclear proteins to their boundaries. Earlier unpublished data by the authors are presented. The "piano playing" hypothesis is suggested based on coordinated active transcription in some of the forum domains and coordinated silencing in the majority of them. The data on the DSB hotspots in human ribosomal DNA gene clusters and their possible association with chromosomal translocations are presented. These clusters are the most actively transcribed DNA regions in cells, as well as the most fragile sites in human chromosomes. The need to revise the available data on DNase I-hypersensitive sites in various genomes, including endogenous DNA breaks of different nature, is discussed.