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Journal article
A Molecular View into the Structure and Dynamics of Phase-Separated Chromatin
The journal of physical chemistry B, v 128(43), pp 10593-10603
16 Oct 2024
PMID: 39413416
Featured in Collection : Research Supported by Drexel Libraries' OA Programs
Abstract
The organization of chromatin is critical for gene expression, yet the underlying mechanisms responsible for this organization remain unclear. Recent work has suggested that phase separation might play an important role in chromatin organization, yet the molecular forces that drive chromatin phase separation are poorly understood. In this work we interrogate a molecular model of chromatin to quantify the driving forces and thermodynamics of chromatin phase separation. By leveraging a multiscale approach, our molecular model is able to reproduce chromatin’s chemical and structural details at the level of nanometers, yet remain efficient enough to simulate chromatin phase separation across 100 nm length scales. We first demonstrate that our model can reproduce key experiments of phase separating nucleosomal arrays, and then apply our model to quantify the interactions that drive their formation into chromatin condensates with either liquid- or solid-like material properties. We next use our model to characterize the molecular structure within chromatin condensates and find that this structure is irregularly ordered and is inconsistent with existing 30 nm fiber models. Lastly we examine how post-translational modifications can modulate chromatin phase separation and how the acetylation of chromatin can lead to chromatin decompaction while still preserving phase separation. Taken together, our work provides a molecular view into the structure and dynamics of phase-separated chromatin and provides new insights into how phase separation might manifest in the nucleus of living cells.
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Details
- Title
- A Molecular View into the Structure and Dynamics of Phase-Separated Chromatin
- Creators
- Joshua Lequieu (Corresponding Author) - Drexel University, Chemical and Biological EngineeringAndrew A Golembeski (Corresponding Author)
- Publication Details
- The journal of physical chemistry B, v 128(43), pp 10593-10603
- Publisher
- ACS Publications
- Number of pages
- 11
- Grant note
- Department of Education: P200A180026 Drexel's University Research Computing Facility - NSF OAC Major Research Infrastructure: 1919691
A.G. was supported by the Department of Education under Award No. P200A180026. This work was also partially supported by a New Investigator Grant from the Charles E. Kaufman Foundation. Simulations were run on hardware supported by Drexel's University Research Computing Facility which is partially funded by NSF OAC Major Research Infrastructure grant #1919691.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Chemical and Biological Engineering
- Web of Science ID
- WOS:001335225900001
- Scopus ID
- 2-s2.0-85208124251
- Other Identifier
- 991021906412104721
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- Web of Science research areas
- Chemistry, Physical