Perspectives: using polymer modeling to understand the formation and function of nuclear compartments

Abstract

Compartmentalization is a ubiquitous feature of cellular function. In the nucleus, early observations revealed a non-random spatial organization of the genome with a large-scale segregation between transcriptionally active—euchromatin—and silenced—heterochromatin—parts of the genome. Recent advances in genome-wide mapping and imaging techniques have strikingly improved the resolution at which nuclear genome folding can be analyzed and have revealed a multiscale spatial compartmentalization with increasing evidences that such compartment may indeed result from and participate to genome function. Understanding the underlying mechanisms of genome folding and in particular the link to gene regulation requires a cross-disciplinary approach that combines the new high-resolution techniques with computational modeling of chromatin and chromosomes. In this perspective article, we first present how the copolymer theoretical framework can account for the genome compartmentalization. We then suggest, in a second part, that compartments may act as a “nanoreactor,” increasing the robustness of either activation or repression by enhancing the local concentration of regulators. We conclude with the need to develop a new framework, namely the “living chromatin” model that will allow to explicitly investigate the coupling between spatial compartmentalization and gene regulation.

Hi-D: Nanoscale mapping of nuclear dynamics in single living cells

“…Heterogeneous chromatin motion arises due to irregular protein binding along the chromosomes and can lead to thermodynamic or electrostatic self-organisation of nuclear compartments [48,49]. Local patches of large anomalous exponents indicate super-diffusive behaviour of chromatin which may result, among others, from thermal and/or active noise acting on the chromatin fiber [50,51], even in quiescent cells.…”

Molecular mechanisms driving transcriptional stress responses

“…Such looping has been reported to occur via CCCTC-binding Factor (CTCF) 94 , cohesin 95 , and Yin-Yang factor 1 (YY1) 96 . Beyond the interactions between protein bound DNA elements, chemical compartmentalization, such as parylation [G] , sumoylation [G] , and phase separation [G] , can create insulated regions (reviewed in 97–99 ), which we discuss here below.…”

Epigenetics of skin cancer: Interventions by selected bioactive phytochemicals

“…Therefore, these epigenetic modifications play a critical role in cell proliferation, differentiation, apoptosis, growth, and development of a cell and an organism including the process of tumorigenesis and metastasis as depicted in Figure . The eukaryotic chromatin network differentiates into the transcriptionally active euchromatin and transcriptionally inactive heterochromatin . The euchromatin region is relatively more diffused and associated with active transcription throughout the cell cycle.…”