 |
 |
GEO help: Mouse over screen elements for information. |
|
| 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 |
| Citation(s) |
38824643 |
| |
| Submission date |
Jul 08, 2022 |
| Last update date |
Aug 16, 2024 |
| 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) |
|
| Relations |
| BioProject |
PRJNA857070 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE207789_RAW.tar |
12.4 Mb |
(http)(custom) |
TAR (of XLSX) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
