Showing papers by "Jekaterina Erenpreisa published in 2021"

Heterochromatin Networks: Topology, Dynamics, and Function (a Working Hypothesis).

Abstract: Open systems can only exist by self-organization as pulsing structures exchanging matter and energy with the outer world. This review is an attempt to reveal the organizational principles of the heterochromatin supra-intra-chromosomal network in terms of nonlinear thermodynamics. The accessibility of the linear information of the genetic code is regulated by constitutive heterochromatin (CHR) creating the positional information in a system of coordinates. These features include scale-free splitting-fusing of CHR with the boundary constraints of the nucleolus and nuclear envelope. The analysis of both the literature and our own data suggests a radial-concentric network as the main structural organization principle of CHR regulating transcriptional pulsing. The dynamic CHR network is likely created together with nucleolus-associated chromatin domains, while the alveoli of this network, including springy splicing speckles, are the pulsing transcription hubs. CHR contributes to this regulation due to the silencing position variegation effect, stickiness, and flexible rigidity determined by the positioning of nucleosomes. The whole system acts in concert with the elastic nuclear actomyosin network which also emerges by self-organization during the transcriptional pulsing process. We hypothesize that the the transcriptional pulsing, in turn, adjusts its frequency/amplitudes specified by topologically associating domains to the replication timing code that determines epigenetic differentiation memory.

A Unified Genomic Mechanism of Cell-Fate Change

Abstract: The purpose of our studies is to elucidate the nature of massive control of whole genome expression with a particular emphasis on cell-fate change. Whole genome expression is coordinated by the emergence of a critical point (CP: a peculiar set of bi-phasic genes) through the genome-engine. In response to stimuli, the genome expression self-organizes three critical states, each exhibiting distinct collective behaviors with its center of mass acting as a local attractor, coexisting with whole genome attractor (GA). Genome-engine mechanism accounts for local attractors interaction in phase space. The CP acts as the organizing center of cell-fate change, and its activation makes local perturbation spread over the genome affecting GA. The activation of CP is in turn elicited by hot-spots, genes with elevated temporal variance, normally in charge to keep genome expression at pace with microenvironment fluctuations. When hot-spots oscillation exceeds a given threshold, the CP synchronizes with the GA driving genome expression state transition. The expression synchronization wave invading the entire genome depends on the power law fusion-bursting dynamics of silencing pericentromere-associated heterochromatin domains and the consequent folding-unfolding status of transcribing euchromatin domains. The proposed mechanism is a unified step toward a time-evolutional transition theory of biological regulation.