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Status |
Public on Mar 14, 2022 |
Title |
Transcriptional regulation of cellular mechanosignaling by PREP1 (PKNOX1) |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Mechanosignaling, initiated by the extracellular physical forces and propagated through the intracellular cytoskeletal network, triggers signaling cascades leading to processes such as embryogenesis, tissue maintenance and disease development. While signal transduction by transcription factors occurs downstream of cellular mechanosensing, nothing is known about the cell intrinsic mechanisms that can regulate mechanosignaling. Here we show that transcription factor PREP1 (PKNOX1) regulates the expression of LINC complex proteins and mechanotransduction of YAP-TAZ. PREP1 depletion upsets the nuclear membrane protein stoichiometry rendering nuclei soft. However, reduced nuclear tension is not conveyed to the cytoplasm, since these cells display fortified actomyosin network with bigger focal adhesion complexes resulting in greater traction forces at the substratum. Intriguingly, YAP-TAZ remains localized to the cytoplasm irrespective of the substrate rigidity indicating disrupted mechanotransduction. Our data demonstrate a hitherto unknown transcriptional mechanism which regulate mechanosignaling upstream of YAP-TAZ transduction.
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Overall design |
Chip-seq analysis of Prep1 (pknox1) binding profiles in human cardiac mesenchymal stromal cells
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Contributor(s) |
Purushothaman D, Bianchi LF, Penkov D, Poli A, Li Q, Pennacchio FA, Pramotton F, Sommariva E, Vermezovic J, Foiani M, Gauthier N, Maiuri P, Blasi F |
Citation(s) |
35550602 |
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Submission date |
Oct 28, 2020 |
Last update date |
May 25, 2022 |
Contact name |
Francesco Blasi |
E-mail(s) |
francesco.blasi@ifom.eu
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Organization name |
IFOM
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Street address |
Via Adamello 16
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City |
Milan |
ZIP/Postal code |
20139 |
Country |
Italy |
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Platforms (1) |
GPL17303 |
Ion Torrent Proton (Homo sapiens) |
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Samples (4)
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Relations |
BioProject |
PRJNA672883 |
SRA |
SRP289444 |
Supplementary file |
Size |
Download |
File type/resource |
GSE160286_RAW.tar |
610.3 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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