Chromatin structure and organization: The relation with gene expression during development and disease

Abstract

The elementary level of chromatin fiber, namely the nucleo filament, is known to undergo a hierarchical compaction leading to local chromatin loops, then chromatin domains and ultimately chromosome territories. These successive folding levels rely on the formation of chromatin loops ranging from few kb to some Mb. In addition to a packaging and structural role, the high-order organization of genomes functionally impacts on gene expression program. This review summarises to which extent each level of chromatin compaction does affect gene regulation. In addition, we point out the structural and functional changes observed in diseases. Emphasis will be mainly placed on the large-scale organization of the chromatin. The genetic material contained in the nucleus has to be transcribed, replicated and repaired all along the cell life, making unlikely the DNA molecules to be haphazardly crammed inside the nucleus. For several decades, evidence has been accumulated showing that the nucleus is highly organized and contains specialized sub-compartments. Several levels of DNA compaction/organization have been depicted: the first and most described one consists in the wrapping of 147 bp around a histone octamer, forming the “bead on a string” or “10 nm” fiber. This elemental level of organization is compacted again in a hierarchical succession of foldings which are all relevant for the understanding of gene expression. In this review, we will mainly focus on the large-scale organization of the chromatin.