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Series GSE207789 Query DataSets for GSE207789
Status Public on Jul 11, 2022
Title FAK is required for suppressing aberrant nuclear mechanotransduction and DNA methylation to prevent vascular injury
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Mechanical forces generated through adhesive interaction of endothelial cells (EC) influence nuclear envelope and thereby gene transcription. Alteration in EC mechanical forces may trigger aberrant gene transcription leading to lethal vascular diseases including acute lung injury (ALI). The intrinsic pathways that instruct EC nuclear-mechanotransduction and thereby maintains vascular homeostasis remain elusive. We have identified focal adhesion kinase (FAK)-mediated mechanotransduction at the nuclear envelope in instructing transcription of EC-barrier protective genes. We show that loss of EC-FAK increases intracellular tension, which in turn activates nuclear envelop protein emerin, and DNA methyltransferase 3a (DNMT3a). Methylation of transcription factor KLF2 promoter by DNMT3a impaired KLF2 synthesis and transcription of the crucial barrier-maintaining gene, S1PR1. Restoring KLF2 or S1PR1 expression or impairing emerin or DNMT3a activity rescued vascular homeostasis in lungs with FAK-deficient or WT-damaged endothelium. Thus, FAK protects against tension-induced aberrant DNA methylation in EC and is a promising target to prevent ALI.
Overall design 2 samples (ATAC-seq)
Contributor(s) Akhter MZ, Yazbeck P, Tauseef M, Anwar M, Datta S, Vellingiri V, Joshi JC, Srivastava N, Lenzini S, Zhou G, Lee J, Jain MK, Shin J, Mehta D
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Submission date Jul 08, 2022
Last update date Jul 12, 2022
Contact name Md Zahid Akhter
Organization name University of Illinois at Chicago
Department Pharmacology & Regenerative Medicine
Lab E-512
Street address 835 S Wolcott Ave
City Chicago
State/province IL
ZIP/Postal code 60612
Country USA
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (2)
GSM6318306 Control
GSM6318307 FAK KO
BioProject PRJNA857070

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE207789_RAW.tar 12.4 Mb (http)(custom) TAR (of XLSX)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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