Potential Role of Phase Separation of Repetitive DNA in Chromosomal Organization

Abstract

The basic principles of chromosomal organization in eukaryotic cells remain elusive. Current mainstream research efforts largely concentrate on searching for critical packaging proteins involved in organizing chromosomes. I have taken a different perspective, by considering the role of genomic information in chromatins. In particular, I put forward the concept that repetitive DNA elements are key chromosomal packaging modules, and their intrinsic property of homology-based interaction can drive chromatin folding. Many repetitive DNA families have high copy numbers and clustered distribution patterns in the linear genomes. These features may facilitate the interactions among members in the same repeat families. In this paper, the potential liquid–liquid phase transition of repetitive DNAs that is induced by their extensive interaction in chromosomes will be considered. I propose that the interaction among repetitive DNAs may lead to phase separation of interacting repetitive DNAs from bulk chromatins. Phase separation of repetitive DNA may provide a physical mechanism that drives rapid massive changes of chromosomal conformation.

Formation of correlated chromatin domains at nanoscale dynamic resolution during transcription

“…Blocks of several A or B compartments tend to interact but their assembly is stochastic and their boundaries cannot be assessed by population averaging Hi-C methods. Domains likely result from auto-assembly ( 61 ) or phase separation-type physical processes driven by accumulation of proteins ( 62 ), such as for example RNA pol II hubs ( 12 ), HP1 droplets ( 63 ) or repeated elements ( 64 ). On the single cell level, sharp boundaries of compartments were also seen in snapshots using super-resolution microscopy ( 65 ).…”

New Aspects of Magnesium Function: A Key Regulator in Nucleosome Self-Assembly, Chromatin Folding and Phase Separation

“…Recently, Tang integrated these self-assembling phenomena and more recent studies including LLPS phenomena into a hypothesis: the interactions occurring among repetitive DNAs may drive the phase separation of these regions from the other chromatin regions [120]. The important point in this hypothesis is that the DNA is the main actor in the phase separation, which is in contrast to the LLPS mechanisms driven by protein interactions and/or protein-RNA interactions.…”

Formation of correlated chromatin domains at nanoscale dynamic resolution during transcription

“…Blocks of several A or B compartments tend to interact but their assembly is stochastic and their boundaries cannot be assessed by population averaging Hi-C methods. Domains likely result from auto assembly(50) or phase separation-type physical processes driven by accumulation of proteins (51), such as for example RNA pol II factories (52), HP1 droplets(53) or repeated elements(54). On the single cell level, sharp boundaries of compartments were also seen in snapshots using super-resolution microscopy(55).Hence, the rough domain boundaries observed in this study are reminiscent of phase transitions, as they separate domains of different dynamic behavior depending on transcriptional activity.…”