Mechanical Regulation of Transcription: Recent Advances

Overview

Journal Trends Cell Biol

Specialty Cell Biology

Date 2021 Mar 13

PMID 33712293

Citations 49

Authors

Kaustubh Wagh

Momoko Ishikawa

David A Garcia

Diana A Stavreva

Arpita Upadhyaya

Gordon L Hager

Affiliations

Soon will be listed here.

Abstract

Mechanotransduction is the ability of a cell to sense mechanical cues from its microenvironment and convert them into biochemical signals to elicit adaptive transcriptional and other cellular responses. Here, we describe recent advances in the field of mechanical regulation of transcription, highlight mechanical regulation of the epigenome as a key novel aspect of mechanotransduction, and describe recent technological advances that could further elucidate the link between mechanical stimuli and gene expression. In this review, we emphasize the importance of mechanotransduction as one of the governing principles of cancer progression, underscoring the need to conduct further studies of the molecular mechanisms involved in sensing mechanical cues and coordinating transcriptional responses.

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References

Das A, Fischer R, Pan D, Waterman C . YAP Nuclear Localization in the Absence of Cell-Cell Contact Is Mediated by a Filamentous Actin-dependent, Myosin II- and Phospho-YAP-independent Pathway during Extracellular Matrix Mechanosensing. J Biol Chem. 2016; 291(12):6096-110. PMC: 4813550. DOI: 10.1074/jbc.M115.708313. View

Panciera T, Azzolin L, Cordenonsi M, Piccolo S . Mechanobiology of YAP and TAZ in physiology and disease. Nat Rev Mol Cell Biol. 2017; 18(12):758-770. PMC: 6192510. DOI: 10.1038/nrm.2017.87. View

Levental K, Yu H, Kass L, Lakins J, Egeblad M, Erler J . Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell. 2009; 139(5):891-906. PMC: 2788004. DOI: 10.1016/j.cell.2009.10.027. View

Plessner M, Melak M, Chinchilla P, Baarlink C, Grosse R . Nuclear F-actin formation and reorganization upon cell spreading. J Biol Chem. 2015; 290(18):11209-16. PMC: 4416828. DOI: 10.1074/jbc.M114.627166. View

Denais C, Gilbert R, Isermann P, McGregor A, Te Lindert M, Weigelin B . Nuclear envelope rupture and repair during cancer cell migration. Science. 2016; 352(6283):353-8. PMC: 4833568. DOI: 10.1126/science.aad7297. View

Asp M, Giacomello S, Larsson L, Wu C, Furth D, Qian X . A Spatiotemporal Organ-Wide Gene Expression and Cell Atlas of the Developing Human Heart. Cell. 2019; 179(7):1647-1660.e19. DOI: 10.1016/j.cell.2019.11.025. View

Kong F, Garcia A, Mould A, Humphries M, Zhu C . Demonstration of catch bonds between an integrin and its ligand. J Cell Biol. 2009; 185(7):1275-84. PMC: 2712956. DOI: 10.1083/jcb.200810002. View

Roy B, Yuan L, Lee Y, Bharti A, Mitra A, Shivashankar G . Fibroblast rejuvenation by mechanical reprogramming and redifferentiation. Proc Natl Acad Sci U S A. 2020; 117(19):10131-10141. PMC: 7229653. DOI: 10.1073/pnas.1911497117. View

Killaars A, Walker C, Anseth K . Nuclear mechanosensing controls MSC osteogenic potential through HDAC epigenetic remodeling. Proc Natl Acad Sci U S A. 2020; 117(35):21258-21266. PMC: 7474590. DOI: 10.1073/pnas.2006765117. View

10.

Quaresma A, Bugai A, Barboric M . Cracking the control of RNA polymerase II elongation by 7SK snRNP and P-TEFb. Nucleic Acids Res. 2016; 44(16):7527-39. PMC: 5027500. DOI: 10.1093/nar/gkw585. View

11.

Kukalev A, Nord Y, Palmberg C, Bergman T, Percipalle P . Actin and hnRNP U cooperate for productive transcription by RNA polymerase II. Nat Struct Mol Biol. 2005; 12(3):238-44. DOI: 10.1038/nsmb904. View

12.

Cooper J, Giancotti F . Integrin Signaling in Cancer: Mechanotransduction, Stemness, Epithelial Plasticity, and Therapeutic Resistance. Cancer Cell. 2019; 35(3):347-367. PMC: 6684107. DOI: 10.1016/j.ccell.2019.01.007. View

13.

Blanchoin L, Boujemaa-Paterski R, Sykes C, Plastino J . Actin dynamics, architecture, and mechanics in cell motility. Physiol Rev. 2014; 94(1):235-63. DOI: 10.1152/physrev.00018.2013. View

14.

Fujiwara S, Baek S, Varticovski L, Kim S, Hager G . High Quality ATAC-Seq Data Recovered from Cryopreserved Breast Cell Lines and Tissue. Sci Rep. 2019; 9(1):516. PMC: 6345852. DOI: 10.1038/s41598-018-36927-7. View

15.

Langhans S . Three-Dimensional Cell Culture Models in Drug Discovery and Drug Repositioning. Front Pharmacol. 2018; 9:6. PMC: 5787088. DOI: 10.3389/fphar.2018.00006. View

16.

Uhler C, Shivashankar G . Regulation of genome organization and gene expression by nuclear mechanotransduction. Nat Rev Mol Cell Biol. 2017; 18(12):717-727. DOI: 10.1038/nrm.2017.101. View

17.

Majewski L, Nowak J, Sobczak M, Karatsai O, Havrylov S, Lenartowski R . Myosin VI in the nucleus of neurosecretory PC12 cells: Stimulation-dependent nuclear translocation and interaction with nuclear proteins. Nucleus. 2018; 9(1):125-141. PMC: 5973263. DOI: 10.1080/19491034.2017.1421881. View

18.

Mistriotis P, Wisniewski E, Bera K, Keys J, Li Y, Tuntithavornwat S . Confinement hinders motility by inducing RhoA-mediated nuclear influx, volume expansion, and blebbing. J Cell Biol. 2019; 218(12):4093-4111. PMC: 6891075. DOI: 10.1083/jcb.201902057. View

19.

Wu J, Lewis A, Grandl J . Touch, Tension, and Transduction - The Function and Regulation of Piezo Ion Channels. Trends Biochem Sci. 2016; 42(1):57-71. PMC: 5407468. DOI: 10.1016/j.tibs.2016.09.004. View

20.

Angulo-Urarte A, van der Wal T, Huveneers S . Cell-cell junctions as sensors and transducers of mechanical forces. Biochim Biophys Acta Biomembr. 2020; 1862(9):183316. DOI: 10.1016/j.bbamem.2020.183316. View