Genomeorganisation

Genome organization refers to the spatial arrangement of genetic material within the nucleus and its relation to genome function. It encompasses how DNA is packaged into chromatin, how chromatin folds within chromosomes, and how the resulting three-dimensional structure influences gene expression, replication timing, and genome integrity.

At the base level, DNA is wrapped around histone proteins to form nucleosomes, which together comprise chromatin. Chromatin is further packaged and organized into distinct chromosome territories, whereby each chromosome occupies a defined region of the nucleus. Within the genome, large-scale compartments reflect functional states: transcriptionally active regions tend to lie in open, decondensed euchromatin (often referred to as compartment A), while repressive, gene-poor regions are found in more condensed heterochromatin (compartment B).

On finer scales, genomes are partitioned into topologically associating domains (TADs) and looping structures that bring distant regulatory elements, such as enhancers and promoters, into close spatial proximity. The formation of these contacts is driven by protein factors including cohesin and CTCF and is influenced by transcription and epigenetic marks. These structures create a regulatory landscape in which gene activity is coordinated within the same domain.

Genome organization also relates to nuclear architecture. Interactions with the nuclear lamina give rise to lamina-associated domains (LADs) that are typically repressive. The arrangement of chromatin and genes affects replication timing and DNA repair, and perturbations can contribute to genome instability and disease.

Genome organization is dynamic and varies across cell types, developmental stages, and environmental conditions. It is studied with methods such as chromosome conformation capture (3C) and Hi-C, as well as fluorescence in situ hybridization (FISH) and related imaging approaches.