Mechanical Determinants of Chromatin Topology and Gene Expression

Overview

Journal Nucleus

Date 2022 Feb 28

PMID 35220881

Authors

Rajiv Kumar Jha

David Levens

Fedor Kouzine

Affiliations

Soon will be listed here.

Abstract

The compaction of linear DNA into micrometer-sized nuclear boundaries involves the establishment of specific three-dimensional (3D) DNA structures complexed with histone proteins that form chromatin. The resulting structures modulate essential nuclear processes such as transcription, replication, and repair to facilitate or impede their multi-step progression and these contribute to dynamic modification of the 3D-genome organization. It is generally accepted that protein-protein and protein-DNA interactions form the basis of 3D-genome organization. However, the constant generation of mechanical forces, torques, and other stresses produced by various proteins translocating along DNA could be playing a larger role in genome organization than currently appreciated. Clearly, a thorough understanding of the mechanical determinants imposed by DNA transactions on the 3D organization of the genome is required. We provide here an overview of our current knowledge and highlight the importance of DNA and chromatin mechanics in gene expression.

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References

Galburt E, Grill S, Wiedmann A, Lubkowska L, Choy J, Nogales E . Backtracking determines the force sensitivity of RNAP II in a factor-dependent manner. Nature. 2007; 446(7137):820-3. DOI: 10.1038/nature05701. View

Pommier Y, Sun Y, Huang S, Nitiss J . Roles of eukaryotic topoisomerases in transcription, replication and genomic stability. Nat Rev Mol Cell Biol. 2016; 17(11):703-721. PMC: 9248348. DOI: 10.1038/nrm.2016.111. View

Uuskula-Reimand L, Hou H, Samavarchi-Tehrani P, Vietri Rudan M, Liang M, Medina-Rivera A . Topoisomerase II beta interacts with cohesin and CTCF at topological domain borders. Genome Biol. 2016; 17(1):182. PMC: 5006368. DOI: 10.1186/s13059-016-1043-8. View

Horberg J, Moreau K, Tamas M, Reymer A . Sequence-specific dynamics of DNA response elements and their flanking sites regulate the recognition by AP-1 transcription factors. Nucleic Acids Res. 2021; 49(16):9280-9293. PMC: 8450079. DOI: 10.1093/nar/gkab691. View

Barutcu A, Blencowe B, Rinn J . Differential contribution of steady-state RNA and active transcription in chromatin organization. EMBO Rep. 2019; 20(10):e48068. PMC: 6776903. DOI: 10.15252/embr.201948068. View

Alexander J, Guan J, Li B, Maliskova L, Song M, Shen Y . Live-cell imaging reveals enhancer-dependent transcription in the absence of enhancer proximity. Elife. 2019; 8. PMC: 6534382. DOI: 10.7554/eLife.41769. View

Nelson P . Transport of torsional stress in DNA. Proc Natl Acad Sci U S A. 1999; 96(25):14342-7. PMC: 24438. DOI: 10.1073/pnas.96.25.14342. View

Gupta P, Zlatanova J, Tomschik M . Nucleosome assembly depends on the torsion in the DNA molecule: a magnetic tweezers study. Biophys J. 2009; 97(12):3150-7. PMC: 2793352. DOI: 10.1016/j.bpj.2009.09.032. View

Soutourina J . Transcription regulation by the Mediator complex. Nat Rev Mol Cell Biol. 2017; 19(4):262-274. DOI: 10.1038/nrm.2017.115. View

10.

Arimura Y, Tachiwana H, Oda T, Sato M, Kurumizaka H . Structural analysis of the hexasome, lacking one histone H2A/H2B dimer from the conventional nucleosome. Biochemistry. 2012; 51(15):3302-9. DOI: 10.1021/bi300129b. View

11.

Ulianov S, Khrameeva E, Gavrilov A, Flyamer I, Kos P, Mikhaleva E . Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains. Genome Res. 2015; 26(1):70-84. PMC: 4691752. DOI: 10.1101/gr.196006.115. View

12.

Brandao H, Gabriele M, Hansen A . Tracking and interpreting long-range chromatin interactions with super-resolution live-cell imaging. Curr Opin Cell Biol. 2020; 70:18-26. PMC: 8364313. DOI: 10.1016/j.ceb.2020.11.002. View

13.

Naughton C, Corless S, Gilbert N . Divergent RNA transcription: a role in promoter unwinding?. Transcription. 2013; 4(4):162-6. PMC: 3977915. DOI: 10.4161/trns.25554. View

14.

Ma J, Wang M . Interplay between DNA supercoiling and transcription elongation. Transcription. 2015; 5(3):e28636. PMC: 4215170. DOI: 10.4161/trns.28636. View

15.

Kaczmarczyk A, Meng H, Ordu O, van Noort J, Dekker N . Chromatin fibers stabilize nucleosomes under torsional stress. Nat Commun. 2020; 11(1):126. PMC: 6949304. DOI: 10.1038/s41467-019-13891-y. View

16.

Kahn J . Topological effects of the TATA box binding protein on minicircle DNA and a possible thermodynamic linkage to chromatin remodeling. Biochemistry. 2000; 39(13):3520-4. DOI: 10.1021/bi992263f. View

17.

Bancaud A, Wagner G, Conde E Silva N, Lavelle C, Wong H, Mozziconacci J . Nucleosome chiral transition under positive torsional stress in single chromatin fibers. Mol Cell. 2007; 27(1):135-47. DOI: 10.1016/j.molcel.2007.05.037. View

18.

Vian L, Pekowska A, Rao S, Kieffer-Kwon K, Jung S, Baranello L . The Energetics and Physiological Impact of Cohesin Extrusion. Cell. 2018; 173(5):1165-1178.e20. PMC: 6065110. DOI: 10.1016/j.cell.2018.03.072. View

19.

Jonkers I, Lis J . Getting up to speed with transcription elongation by RNA polymerase II. Nat Rev Mol Cell Biol. 2015; 16(3):167-77. PMC: 4782187. DOI: 10.1038/nrm3953. View

20.

Banigan E, Mirny L . Loop extrusion: theory meets single-molecule experiments. Curr Opin Cell Biol. 2020; 64:124-138. DOI: 10.1016/j.ceb.2020.04.011. View