 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jun 01, 2019 |
| Title |
De-differentiation by Adenovirus E1A Due to Inactivation of Hippo Pathway Effectors YAP and TAZ [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Adenovirus-transformed cells have a de-differentiated phenotype. Eliminating E1A in transformed human embryonic kidney cells de-repressed ~2600 genes, generating a gene expression profile closely resembling mesenchymal stem cells (MSC). This was associated with a dramatic change in cell morphology from one with scant cytoplasm and a globular nucleus to one with increased cytoplasm, extensive actin stress fibers and actomyosin-dependent flattening against the substratum. E1A-induced histone hypoacetylation by p300/CBP at H3K27/18 was reversed. Most of the increase in H3K27/18ac was near TEAD transcription factors associated with their co-activators YAP and TAZ regulated by the Hippo pathway. E1A causes YAP/TAZ cytoplasmic sequestration. After eliminating E1A, YAP/TAZ were transported into nuclei where they associated with poised enhancers with DNA-bound TEAD4 and H3K4me1. This activation of YAP/TAZ required RHO-family GTPase signaling and caused histone acetylation by p300/CBP, chromatin remodeling, and cohesin loading to establish MSC-associated enhancers and then super-enhancers. Consistent results were also observed in rat embryo kidney cells, human fibroblasts and human respiratory tract epithelial cells. These results together with earlier studies suggest that YAP/TAZ function in a developmental check-point controlled by signaling from the actin cytoskeleton that prevents differentiation of a progenitor cell until it is in the correct cellular and tissue environment.
|
| |
|
| Overall design |
Examination of YAP, H3K18ac, H3K27ac, H3K4me1, TEAD1, TEAD4, RAD21, chromatin accessibility and mRNA by ChIP-seq, ATAC-seq, and mRNA-seq
|
| |
|
| Contributor(s) |
Zemke NR, Berk A |
| Citation(s) |
31171701 |
| |
| Submission date |
Apr 22, 2019 |
| Last update date |
Aug 31, 2019 |
| Contact name |
Bing Ren |
| E-mail(s) |
biren@health.ucsd.edu
|
| Organization name |
UCSD
|
| Street address |
9500 Gilman Drive
|
| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92093 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
|
| Samples (44)
|
|
| This SubSeries is part of SuperSeries: |
| GSE130137 |
De-differentiation by Adenovirus E1A Due to Inactivation of Hippo Pathway Effectors YAP and TAZ |
|
| Relations |
| BioProject |
PRJNA534076 |
| SRA |
SRP193327 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE130135_RAW.tar |
4.8 Gb |
(http)(custom) |
TAR (of BIGWIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
Less...
More...