Beyond Chaperoning: The Multifaceted Role of FACT in Chromatin Transactions
Abstract
1. Introduction
2. Structural Organization of the hFACT Chaperone
3. Physiological Functions of FACT
3.1. FACT in Transcription: Dynamic Regulation of Chromatin for Gene Expression
3.2. FACT Complex in DNA Replication: Maintaining Chromatin Integrity
3.3. FACT Complex and Post-Translational Modifications: A Dynamic Regulatory Network
3.4. FACT Complex in DNA Damage Repair: Chromatin Reorganization for Genome Stability
4. FACT Complex in Chromatin Homeostasis
4.1. A Master Regulator of Nucleosome Dynamics
4.2. Nucleosome Recognition and Reorganization by the FACT Complex
4.3. Mechanisms of Nucleosome Unfolding by FACT: Structural Insights
- (1)
- Initial engagement through asymmetric contacts with histones and DNA;
- (2)
- Local DNA distortion leading to partial unwrapping;
- (3)
- Stabilization of a metastable unfolded state.
4.4. FACT Complex as a Chromatin Plasticity Modulator in Cell Identity Transitions (Cell Fate Determination)
4.5. Perspectives and Unresolved Questions in FACT-Mediated Nucleosome Unfolding
- (1)
- How does FACT coordinate with other chromatin remodelers in vivo given its unique histone-retention mechanism?
- (2)
- Does partial unfolding represent the endpoint or intermediate in physiological contexts?
- (3)
- How do post-translational modifications alter FACT unfolding energetics?
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
FACT | Facilitates Chromatin Transcription |
SPT16 | Suppressor of Ty 16 |
SSRP1 | Structure Specific Recognition Protein 1 |
HMG | High-mobility group |
FRET | Fluorescence Resonance Energy Transfer |
NTD | N-terminal domain |
Cryo-EM | Cryoelectron microscopy |
MCM | Minichromosome maintenance |
PTM | Post-translational modifications |
CK2 | Casein kinase 2 |
RNAP | RNA polymerase |
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Volokh, O.; Studitsky, V.M.; Sokolova, O.S. Beyond Chaperoning: The Multifaceted Role of FACT in Chromatin Transactions. Int. J. Mol. Sci. 2025, 26, 5176. https://doi.org/10.3390/ijms26115176
Volokh O, Studitsky VM, Sokolova OS. Beyond Chaperoning: The Multifaceted Role of FACT in Chromatin Transactions. International Journal of Molecular Sciences. 2025; 26(11):5176. https://doi.org/10.3390/ijms26115176
Chicago/Turabian StyleVolokh, Olesya, Vasily M. Studitsky, and Olga S. Sokolova. 2025. "Beyond Chaperoning: The Multifaceted Role of FACT in Chromatin Transactions" International Journal of Molecular Sciences 26, no. 11: 5176. https://doi.org/10.3390/ijms26115176
APA StyleVolokh, O., Studitsky, V. M., & Sokolova, O. S. (2025). Beyond Chaperoning: The Multifaceted Role of FACT in Chromatin Transactions. International Journal of Molecular Sciences, 26(11), 5176. https://doi.org/10.3390/ijms26115176