Liquid-liquid phase separation (LLPS) in DNA and chromatin systems from the perspective of colloid physical chemistry
(2024) In Advances in Colloid and Interface Science 326.- Abstract
DNA is a highly charged polyelectrolyte and is prone to associative phase separation driven by the presence of multivalent cations, charged surfactants, proteins, polymers and colloids. The process of DNA phase separation induced by positively charged species is often called DNA condensation. Generally, it refers to either intramolecular DNA compaction (coil-globule transition) or intermolecular DNA aggregation with macroscopic phase separation, but the formation of a DNA liquid crystalline system is also displayed. This has traditionally been described by polyelectrolyte theory and qualitative (Flory-Huggins-based) polymer theory approaches. DNA in the cell nucleus is packed into chromatin wound around the histone octamer (a protein... (More)
DNA is a highly charged polyelectrolyte and is prone to associative phase separation driven by the presence of multivalent cations, charged surfactants, proteins, polymers and colloids. The process of DNA phase separation induced by positively charged species is often called DNA condensation. Generally, it refers to either intramolecular DNA compaction (coil-globule transition) or intermolecular DNA aggregation with macroscopic phase separation, but the formation of a DNA liquid crystalline system is also displayed. This has traditionally been described by polyelectrolyte theory and qualitative (Flory-Huggins-based) polymer theory approaches. DNA in the cell nucleus is packed into chromatin wound around the histone octamer (a protein complex comprising two copies each of the four histone proteins H2A, H2B, H3 and H4) to form nucleosomes separated by linker DNA. During the last decade, the phenomenon of the formation of biomolecular condensates (dynamic droplets) by liquid-liquid phase separation (LLPS) has emerged as a generally important mechanism for the formation of membraneless organelles from proteins, nucleic acids and their complexes. DNA and chromatin droplet formation through LLPS has recently received much attention by in vitro as well as in vivo studies that established the importance of this for compartmentalisation in the cell nucleus. Here, we review DNA and chromatin LLPS from a general colloid physical chemistry perspective. We start with a general discussion of colloidal phase separation in aqueous solutions and review the original (pre-LLPS era) work on DNA (macroscopic) phase separation for simpler systems with DNA in the presence of multivalent cations and well-defined surfactants and colloids. Following that, we discuss and illustrate the similarities of such macroscopic phase separation with the general behaviour of LLPS droplet formation by associative phase separation for DNA-protein systems, including chromatin; we also note cases of segregative association. The review ends with a discussion of chromatin LLPS in vivo and its physiological significance.
(Less)
- author
- Nordenskiöld, Lars ; Shi, Xiangyan ; Korolev, Nikolay ; Zhao, Lei ; Zhai, Ziwei and Lindman, Björn LU
- organization
- publishing date
- 2024-04
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Biomolecular condensates, DNA condensation, DNA-protein interactions, Dynamic droplets, Polyelectrolyte effects, Surfactants
- in
- Advances in Colloid and Interface Science
- volume
- 326
- article number
- 103133
- publisher
- Elsevier
- external identifiers
-
- pmid:38547652
- scopus:85188955177
- ISSN
- 0001-8686
- DOI
- 10.1016/j.cis.2024.103133
- language
- English
- LU publication?
- yes
- id
- 3d2a989a-200d-4022-a2d4-1352b4ef7400
- date added to LUP
- 2024-04-18 09:39:11
- date last changed
- 2024-04-19 03:00:07
@article{3d2a989a-200d-4022-a2d4-1352b4ef7400,
abstract = {{<p>DNA is a highly charged polyelectrolyte and is prone to associative phase separation driven by the presence of multivalent cations, charged surfactants, proteins, polymers and colloids. The process of DNA phase separation induced by positively charged species is often called DNA condensation. Generally, it refers to either intramolecular DNA compaction (coil-globule transition) or intermolecular DNA aggregation with macroscopic phase separation, but the formation of a DNA liquid crystalline system is also displayed. This has traditionally been described by polyelectrolyte theory and qualitative (Flory-Huggins-based) polymer theory approaches. DNA in the cell nucleus is packed into chromatin wound around the histone octamer (a protein complex comprising two copies each of the four histone proteins H2A, H2B, H3 and H4) to form nucleosomes separated by linker DNA. During the last decade, the phenomenon of the formation of biomolecular condensates (dynamic droplets) by liquid-liquid phase separation (LLPS) has emerged as a generally important mechanism for the formation of membraneless organelles from proteins, nucleic acids and their complexes. DNA and chromatin droplet formation through LLPS has recently received much attention by in vitro as well as in vivo studies that established the importance of this for compartmentalisation in the cell nucleus. Here, we review DNA and chromatin LLPS from a general colloid physical chemistry perspective. We start with a general discussion of colloidal phase separation in aqueous solutions and review the original (pre-LLPS era) work on DNA (macroscopic) phase separation for simpler systems with DNA in the presence of multivalent cations and well-defined surfactants and colloids. Following that, we discuss and illustrate the similarities of such macroscopic phase separation with the general behaviour of LLPS droplet formation by associative phase separation for DNA-protein systems, including chromatin; we also note cases of segregative association. The review ends with a discussion of chromatin LLPS in vivo and its physiological significance.</p>}},
author = {{Nordenskiöld, Lars and Shi, Xiangyan and Korolev, Nikolay and Zhao, Lei and Zhai, Ziwei and Lindman, Björn}},
issn = {{0001-8686}},
keywords = {{Biomolecular condensates; DNA condensation; DNA-protein interactions; Dynamic droplets; Polyelectrolyte effects; Surfactants}},
language = {{eng}},
publisher = {{Elsevier}},
series = {{Advances in Colloid and Interface Science}},
title = {{Liquid-liquid phase separation (LLPS) in DNA and chromatin systems from the perspective of colloid physical chemistry}},
url = {{http://dx.doi.org/10.1016/j.cis.2024.103133}},
doi = {{10.1016/j.cis.2024.103133}},
volume = {{326}},
year = {{2024}},
}