|
| Status |
Public on Nov 14, 2020 |
| Title |
ZNF416 is a pivotal transcriptional regulator of fibroblast mechano-activation [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Matrix stiffness is a central regulator of fibroblast function. However, the transcriptional mechanisms linking matrix stiffness to changes in fibroblast phenotype are incompletely understood. Here, we evaluated the effect of matrix stiffness on genome-wide chromatin accessibility in freshly-isolated lung fibroblasts using ATAC-seq. We found higher matrix stiffness profoundly increased global chromatin accessibility relative to lower matrix stiffness, and these alterations were in close genomic proximity to known pro-fibrotic gene programs. Motif analysis of these regulated genomic loci identified ZNF416 as a putative mediator of fibroblast stiffness responses. Genome occupancy analysis using ChIP-seq confirmed that ZNF416 occupies a broad range of genes implicated in fibroblast activation and tissue-fibrosis, with relatively little overlap in genomic occupancy with other mechanoresponsive and pro-fibrotic transcriptional regulators. Using loss and gain of function studies we demonstrated that ZNF416 plays a critical role in fibroblast proliferation, extracellular matrix synthesis and contractile function. Together these observations identify ZNF416 as novel mechano-activated transcriptional regulator of fibroblast biology.
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| |
|
| Overall design |
ChIPseq of ZNF416-FLAG in primary human lung fibroblasts
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| |
|
| Contributor(s) |
Jones DL, Tschumperlin DJ |
| Citation(s) |
33625469 |
| Submission date |
Nov 13, 2020 |
| Last update date |
Jun 22, 2022 |
| Contact name |
Aditya Bhagwate |
| E-mail(s) |
bhagwate.adityavijay@mayo.edu
|
| Organization name |
Mayo Clinic
|
| Street address |
200 1st Street SW
|
| City |
Rochester |
| State/province |
MN |
| ZIP/Postal code |
55905 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
|
| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE161448 |
ZNF416 is a pivotal transcriptional regulator of fibroblast mechano-activation |
|
| Relations |
| BioProject |
PRJNA678324 |
| SRA |
SRP292514 |
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