title: Transcription upregulation via force-induced direct stretching of chromatin.
abstract: Mechanical forces play critical roles in the function of living cells. However, the underlying mechanisms of how forces influence nuclear events remain elusive. Here, we show that chromatin deformation as well as force-induced transcription of a green fluorescent protein (GFP)-tagged bacterial-chromosome dihydrofolate reductase (DHFR) transgene can be visualized in a living cell by using three-dimensional magnetic twisting cytometry to apply local stresses on the cell surface via an Arg-Gly-Asp-coated magnetic bead. Chromatin stretching depended on loading direction. DHFR transcription upregulation was sensitive to load direction and proportional to the magnitude of chromatin stretching. Disrupting filamentous actin or inhibiting actomyosin contraction abrogated or attenuated force-induced DHFR transcription, whereas activating endogenous contraction upregulated force-induced DHFR transcription. Our findings suggest that local stresses applied to integrins propagate from the tensed actin cytoskeleton to the LINC complex and then through lamina-chromatin interactions to directly stretch chromatin and upregulate transcription.
authors.affiliation: Laboratory for Cellular Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.|Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Arash
authors.identifier: http://orcid.org/0000-0003-1001-7351
authors.initials: A
authors.lastname: Tajik
authors.affiliation: Laboratory for Cellular Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
authors.forename: Yuejin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Laboratory for Cellular Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
authors.forename: Fuxiang
authors.initials: F
authors.lastname: Wei
authors.affiliation: Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Laboratory for Cellular Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Jia
authors.affiliation: Laboratory for Cellular Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Rishi
authors.initials: R
authors.lastname: Singh
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Nimish
authors.initials: N
authors.lastname: Khanna
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Belmont
authors.affiliation: Laboratory for Cellular Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.|Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D016466:CHO Cells; D002470:Cell Survival; D002843:Chromatin / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D003599:Cytoskeleton / Q000378:metabolism; D005786:Gene Expression Regulation; D055595:Mechanical Phenomena; D015530:Nuclear Matrix / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin