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Spatiotemporal organization of the subnuclear medium plays a crucial role in genome regulation
[1]. However, the effect of active perturbation from various molecular actions in the medium on
this organization remains unclear. In this seminar, I will mainly focus on our recent investigations
into how such activities influence the coordination of subnuclear compartments (SNCs, such as
transcription factories) with chromatin and the compartmentalization of chromatin into eu- and
heterochromatic regions, and discuss their biological implications.
We have developed a polymer physics-based computational framework where chromatin is
perturbed by a non-localized active mechanism mimicking the action of Topoisomerase-II enzyme.
Using a self-developed GPU-based parallelized computer code and a newly introduced theoretical
model, we demonstrate that SNC dynamics in this complex system can be described by a
combination of three modes, each linked to different physical aspects of the embedding medium.
Notably, the activity enhances SNC dynamics through a slow mode associated with chromatin-mesh
remodeling. This offers new insights into the role of global active perturbations in target-searching
processes [2].
Additionally, we report the emergence of characteristic compartmentalization features, viz.,
wall-like organization of euchromatin with negative nematic ordering of the euchromatic segments
due to activity. These features cannot be captured by an equilibrium physics-based theory. This
highlights the critical role of such active perturbations in chromatin organization [3]. Given that
activity correlates with factors like aging and cell cycle, our studies may shed light on cell state-
specific genome regulation.
I will conclude my seminar with a brief discussion of my future research plan on ‘Integrative
Nuclear Architecture’, which investigates the spatiotemporal characteristics of the nucleus as
collective features arising from interconnected cellular components.
References:
1. Job Dekker et al., The 4D nucleome project, Nature 549, 219 (2017).
2. RD, Takahiro Sakaue, G. V. Shivashankar, Jacques Prost, and Tetsuya Hiraiwa, Chromatin
remodeling due to transient-link-and-pass activity enhances subnuclear dynamics, Phys.
Rev. Lett. 132, 058401 (2024).
3. RD, Takahiro Sakaue, G. V. Shivashankar, Jacques Prost, and Tetsuya Hiraiwa, How
enzymatic activity is involved in chromatin organization, eLife 11, e79901 (2022). |