Structure-driven homology pairing of chromatin fibers: the role of electrostatics and protein-induced bridging

Abstract

Chromatin domains formed in vivo are characterized by different types of 3D organization of interconnected nucleosomes and architectural proteins. Here, we quantitatively test a hypothesis that the similarities in the structure of chromatin fibers (which we call "structural homology") can affect their mutual electrostatic and protein-mediated bridging interactions. For example, highly repetitive DNA sequences in heterochromatic regions can position nucleosomes so that preferred inter-nucleosomal distances are preserved on the surfaces of neighboring fibers. On the contrary, the segments of chromatin fiber formed on unrelated DNA sequences have different geometrical parameters and lack structural complementarity pivotal for stable association and cohesion. Furthermore, specific functional elements such as insulator regions, transcription start and termination sites, and replication origins are characterized by strong nucleosome ordering that might induce structure-driven iterations of chromatin fibers. We propose that shape-specific protein-bridging interactions facilitate long-range pairing of chromatin fragments, while for closely-juxtaposed fibers electrostatic forces can in addition yield fine-tuned structurespecific recognition and pairing. These pairing effects can account for some features observed for mitotic and inter-phase chromatins.

Excluded volume effect enhances the homology pairing of model chromosomes

“…It should be noted that homologous loci can often be bound by the electrostatic forces or the bindings of DNA-bridging proteins if these regions are sufficiently close, as mentioned in recent studies [1][2][3][4][5][6][7][8][9]. Thus, if homologous chromosomes are close enough for an appropriately long period of time, as observed in the present results for large W values, the synapsis of homologous loci can form with a sufficiently high probability.…”

“…This process requires synapsis formation between homologous loci along the lengths of maternal and paternal chromosomes. Recent theoretical studies suggest that the homologies of the sequence-dependent distributions of the electrostatic charge and the binding sites of DNA-bridging proteins play important roles in the recognition and pairing of homologous loci [1][2][3][4][5][6][7][8][9].…”

Structures and functions in the crowded nucleus: new biophysical insights

“…Reports that nucleosomes which contain identical DNA sequences can self-associate preferentially [85] raise the possibility that similar interactions could contribute to the formation and stabilization of loops [86]. Could this be one of the still obscure functions of "junk" DNA [87]?…”

Identification of peculiar and common effects of histone modifications on transcription

“…They exert this effect by modulating local chromatin structure and thereby changing the accessibility of TFs. As a matter of fact, some other factors can also shape chromatin and then control gene activity, such as the electrostatic effect and concentration of H1 histone, DNA sequence, and long-range internucleosome interactions, which influence DNA compaction by regulating the distance between two neighboring nucleosomes, namely nucleosome repeat length (NRL) (Beshnova et al, 2014;Cherstvy and Teif, 2014), and the similarities in the structure of chromatin fibers (structural homology), which affect their pairing by electrostatic and protein-mediated bridging interactions (Cherstvy and Teif, 2013). Because of the close relationship between these factors and DNA structure, it is possible to construct a model predicting gene transcription level by them, too.…”