title: The mammalian LINC complex regulates genome transcriptional responses to substrate rigidity.
abstract: Mechanical integration of the nucleus with the extracellular matrix (ECM) is established by linkage between the cytoskeleton and the nucleus. This integration is hypothesized to mediate sensing of ECM rigidity, but parsing the function of nucleus-cytoskeleton linkage from other mechanisms has remained a central challenge. Here we took advantage of the fact that the LINC (linker of nucleoskeleton and cytoskeleton) complex is a known molecular linker of the nucleus to the cytoskeleton, and asked how it regulates the sensitivity of genome-wide transcription to substratum rigidity. We show that gene mechanosensitivity is preserved after LINC disruption, but reversed in direction. Combined with myosin inhibition studies, we identify genes that depend on nuclear tension for their regulation. We also show that LINC disruption does not attenuate nuclear shape sensitivity to substrate rigidity. Our results show for the first time that the LINC complex facilitates mechano-regulation of expression across the genome.
authors.affiliation: Department of Chemical Engineering, University of Florida, Bldg. 723, Gainesville, FL 32611, USA.
authors.forename: Samer G
authors.initials: SG
authors.lastname: Alam
authors.affiliation: Department of Chemical Engineering, University of Florida, Bldg. 723, Gainesville, FL 32611, USA.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: HudsonAlpha Institute of Biotechnology, Huntsville, AL, 35806, USA.
authors.forename: Nripesh
authors.initials: N
authors.lastname: Prasad
authors.affiliation: Department of Chemical Engineering, University of Florida, Bldg. 723, Gainesville, FL 32611, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biology, University of Florida, Cancer and Genetics Research Complex, 2033 Mowry Road, Gainesville, FL 32610, USA.
authors.forename: Srikar
authors.initials: S
authors.lastname: Chamala
authors.affiliation: Department of Chemical Engineering, University of Florida, Bldg. 723, Gainesville, FL 32611, USA.
authors.forename: Ram
authors.initials: R
authors.lastname: Kuchibhotla
authors.affiliation: Sanford Children's Health Research Center, Sanford Research, Sioux Falls, SD 57104, USA, Gainesville, FL 32610, USA.
authors.forename: Birendra
authors.initials: B
authors.lastname: Kc
authors.affiliation: Department of Chemical Engineering, University of Florida, Bldg. 723, Gainesville, FL 32611, USA.
authors.forename: Varun
authors.initials: V
authors.lastname: Aggarwal
authors.affiliation: HudsonAlpha Institute of Biotechnology, Huntsville, AL, 35806, USA.|Department of Biological Sciences, University of Alabama in Huntsville, Huntsville, AL 35186, USA.
authors.forename: Shristi
authors.initials: S
authors.lastname: Shrestha
authors.affiliation: HudsonAlpha Institute of Biotechnology, Huntsville, AL, 35806, USA.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Jones
authors.affiliation: HudsonAlpha Institute of Biotechnology, Huntsville, AL, 35806, USA.
authors.forename: Shawn E
authors.initials: SE
authors.lastname: Levy
authors.affiliation: Sanford Children's Health Research Center, Sanford Research, Sioux Falls, SD 57104, USA, Gainesville, FL 32610, USA.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Roux
authors.affiliation: Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Nickerson
authors.affiliation: Department of Chemical Engineering, University of Florida, Bldg. 723, Gainesville, FL 32611, USA.
authors.forename: Tanmay P
authors.initials: TP
authors.lastname: Lele
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D012333:RNA, Messenger / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger