Navigating the crowd: visualizing coordination between genome dynamics, structure, and transcription

Abstract

The eukaryotic genome is hierarchically structured yet highly dynamic. Regulating transcription in this environment demands a high level of coordination to permit many proteins to interact with chromatin fiber at appropriate sites in a timely manner. We describe how recent advances in quantitative imaging techniques overcome caveats of sequencing-based methods (Hi-C and related) by enabling direct visualization of transcription factors and chromatin at high resolution, from single genes to the whole nucleus. We discuss the contribution of fluorescence imaging to deciphering the principles underlying this coordination within the crowded nuclear space in living cells and discuss challenges ahead.

Spatial organization of chromosomes leads to heterogeneous chromatin motion and drives the liquid- or gel-like dynamical behavior of chromatin

“…Beyond the 'static' picture of a layered spatial organization that contributes to genome regulation, more and more experiments on living cells highlighted the 'dynamic' nature of chromatin folding and its importance on key biological functions (Tortora et al 2020;Bystricky 2015;Shaban et al 2020a). Chromatin mobility has been proposed to impact the dynamics of promoter-enhancer interactions and thus regulates transcriptional bursting (Bartman et al 2016;Chen et al 2018), facilitates homology search after DNA damage (Hauer et al 2017) or participates in the long-range spreading of epigenomic marks (Jost and Vaillant 2018).…”

Towards the Idea of Molecular Brains

“…Once folded, each protein moves and vibrates according to its type of folding, its sequence and its partners [ 200 , 201 , 202 ]. There is then a gradation of movements from the dynamics of a single protein to the concerted and synchronised movements of a large number of partners in macromolecular complexes during replication, transcription and translation [ 203 , 204 , 205 ]. Moreover, all these processes are coupled and interdependent.…”

Genome Organization and Dynamics Specialty Grand Challenge

“…While early electron micrographs supported the contention that chromosomes from bacteria to humans are differentially compacted within a cell (Alberts et al, 2002), it wasn't until the development of advanced microscopy and molecular techniques that we were able to visualize the intricate organization of all genomes. Groundbreaking advances in super resolution microscopy have enabled unprecedented views of genomes within the three-dimensional space of whole cells leading to the discovery of chromosome territories and the monitoring of directed, long-distance chromatin movements within live interphase cells (Shaban et al, 2020). Novel molecular approaches, especially techniques based on the chromatin conformation capture (3C) assay, have validated the concept of select chromosome packaging and extended our resolution of the organization to the single base pair level (Dekker and Misteli 2015).…”