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

Jekaterina Erenpreisa,Talivaldis Freivalds,Alessandro Giuliani,Pawel Zayakin,Bogdan I Gerashchenko,Reet Kurg,Kristine Salmina,Matthias Krufczik,Ruth Winter,Jekabs Krigerts,Michael Hausmann

doi:10.3390/cells10071582

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.

Highlights

The DNA linear sequence code represents only the most basic principle of gene regulation
The available molecular and morphological data indicate that most Nucleolus-Associated Domains (NADs) are associated with pericentromere-associated domains (PADs), and this link can be hypothesized to play a role in the formation of functional alveoli and scale-free transcriptional pulsing of their mutual network coordinating rRNA and mRNA synthesis in the radially directed relay
We applied an empirical approach for the revelation of the constitutive heterochromatin network showing similar features in different animals and cell types

Summary

Introduction

The DNA linear sequence code represents only the most basic principle of gene regulation. The three main properties of CHR—the position variegation effect, stickiness [32,33], and flexible rigidity [23,29,34]—are important for its network-related genome regulation and the prerequisite for network formation These properties of CHR are consistent with the earlier ideas that heterochromatin topology, in terms of the sum of its position-cissilencing effects on transcription, can provide the 3D “genome active space” in addition to the DNA gene-coding function, “the morphogenic function” [35]—a source of positional information necessary for the whole genome regulation [8,36,37,38,39,40,41,42]. To support the general aspects in detail, we will present some data on heterochromatin network visualization and features obtained by image analysis and their functional-structural changes associated with developmental and transcription shifts available from the literature and our own data

Visualization of the Supra-Chromosomal Networks

Dynamics of the Heterochromatin Network

Transcriptional Pulsing and Synchronization in a Cell Population

Findings

10. Conclusions