Abstract
Eukaryotic genomes contain a large amount of DNA repeats (also known as repetitive DNA, repetitive elements, and repetitive sequences). Here, I propose a role of repetitive DNA in the formation of higher-order structures of chromosomes. The central idea of this theory is that chromatin regions with repetitive sequences pair with regions harboring homologous repeats and that such somatic repeat pairing (RP) assembles repetitive DNA chromatin into compact chromosomal domains that specify chromatin folding in a site-directed manner. According to this theory, DNA repeats are not randomly distributed in the genome. Instead, they form a core framework that coordinates the architecture of chromosomes. In contrast to the viewpoint that DNA repeats are genomic ‘junk’, this theory advocates that repetitive sequences are chromatin organizer modules that determine chromatin-chromatin contact points within chromosomes. This novel concept, if correct, would suggest that DNA repeats in the linear genome encode a blueprint for higher-order chromosomal organization.
Highlights
In humans and other higher organisms, repetitive DNA sequences make up more than 50% of the genome [1,2,3]
This paper focuses on the potential role of repeat pairing (RP) in chromatin organization, RP is probably a genomic event with broad functional implications and may provide a general conceptual framework for understanding the diverse biological activities proposed for specific repeats [7,8]
Because of RP, DNA repeats are assembled into core clusters (RAs) that coordinate chromatin folding
Summary
In humans and other higher organisms, repetitive DNA sequences make up more than 50% of the genome [1,2,3]. The undisputed phenomenon of somatic homologous pairing, as outlined above, strongly suggests the existence of molecular and cellular mechanisms that support the recognition and interaction of chromatin regions with homologous DNA sequences. Bearing with this notion, I propose that chromatin loci with repeats that are in the same family interact in the cell and term this type of chromatin interaction ‘repeat pairing’ (RP). Multiple lines of evidence support the idea of RP of repetitive DNA in the cells This is most clearly indicated by the spatial clustering of dispersed repeats. It is intriguing to envision that they have evolved to cluster in different cell states and generate physiologically relevant chromosomal conformations (see below)
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