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| Status |
Public on Jun 01, 2019 |
| Title |
De-differentiation by Adenovirus E1A Due to Inactivation of Hippo Pathway Effectors YAP and TAZ [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| 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.
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| Overall design |
Examination of YAP, H3K18ac, H3K27ac, H3K4me1, TEAD1, TEAD4, RAD21, chromatin accessibility and mRNA by ChIP-seq, ATAC-seq, and mRNA-seq
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| Contributor(s) |
Zemke NR, Berk A |
| Citation(s) |
31171701 |
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| Submission date |
Apr 22, 2019 |
| Last update date |
Aug 31, 2019 |
| Contact name |
Bing Ren |
| E-mail(s) |
biren@health.ucsd.edu
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| Organization name |
UCSD
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| Street address |
9500 Gilman Drive
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92093 |
| Country |
USA |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (23)
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| This SubSeries is part of SuperSeries: |
| GSE130137 |
De-differentiation by Adenovirus E1A Due to Inactivation of Hippo Pathway Effectors YAP and TAZ |
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| Relations |
| BioProject |
PRJNA534074 |
| SRA |
SRP193326 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE130136_RAW.tar |
2.4 Gb |
(http)(custom) |
TAR (of BIGWIG) |
| GSE130136_cuffdiff_out_all_genes_siCtrl_or_siE1A_4d_8d_16d.txt.gz |
882.1 Kb |
(ftp)(http) |
TXT |
| GSE130136_cuffdiff_out_all_genes_siCtrl_siYAP_siTAZ_siYT_siE1A_siEY_siET_siEYT.txt.gz |
641.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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