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| Status |
Public on May 01, 2024 |
| Title |
Human cytomegalovirus infection coopts chromatin organization to modulate TEAD1 transcription factor activity [ATAC-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Human cytomegalovirus (HCMV) infects up to 80% of the world’s population and is linked to serious morbidity in immunocompromised individuals and newborns. Here, using multiple genome-scale assays and computational approaches, we show that HCMV infection leads to widespread changes in chromatin accessibility and chromatin looping, with hundreds of thousands of human genomic regions affected 48 hours after infection. Integrative analyses reveal that HCMV infection perturbs the Hippo signaling pathway by drastically diminishing TEA domain transcription factor 1 (TEAD1) activity. Chromatin immunoprecipitation experiments confirm extensive concordant loss of TEAD1 binding and H3K27ac active histone marks upon infection. TEAD transcription factors are direct effectors of the Hippo signaling pathway, and our data support a position for TEAD1 at the top of a hierarchy involving key developmental pathways with differential expression subsequent to HMCV infection. Known gene targets of TEAD1, including Cellular Communication Network Factor 1 (CCN1) and Thrombospondin 1 (THBS1), are significantly downregulated with HCMV infection, reflecting diminished TEAD1-mediated activity. HCMV infection reduces TEAD1 binding through four distinct mechanisms: closing of TEAD1-bound chromatin, reduction of Yes1 associated transcriptional regulator (YAP1) and phosphorylated YAP (pYAP1) levels, reduction of TEAD1 transcript and protein levels, and alteration of TEAD1 exon-6 usage. Collectively, these comprehensive genome-scale analyses reveal novel mechanisms induced by HCMV infection.
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| Overall design |
We performed ATAC-seq in two human cell lines in two conditions. The cell lines are foreskin fibroblasts (HS68) and retinal epithelial (ARPE-19). The two conditions are: 1) uninfected; and 2) 48 hours post infection of human cytomegalovirus (HCMV) with the TB40/E clinical isolate. Experiments were performed in two replicates for each cell type and condition combination.
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| Contributor(s) |
Weirauch M, Kottyan L |
| Citation(s) |
38645179 |
| Submission date |
Jan 31, 2024 |
| Last update date |
May 03, 2024 |
| Contact name |
Matthew Weirauch |
| E-mail(s) |
Matthew.Weirauch@cchmc.org
|
| Organization name |
Cincinnati Children's Hospital Medical Center
|
| Department |
Center for Autoimmune Genomics and Etiology (CAGE)
|
| Street address |
3333 Burnet Avenue
|
| City |
Cincinnati |
| State/province |
Ohio |
| ZIP/Postal code |
45229-3026 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (8)
|
| GSM8056978 |
ATAC-seq: HS68 HCMV-infected Replicate 2 |
| GSM8056979 |
ATAC-seq: ARPE-19 Uninfected Replicate 1 |
| GSM8056980 |
ATAC-seq: ARPE-19 Uninfected Replicate 2 |
| GSM8056981 |
ATAC-seq: ARPE-19 HCMV-infected Replicate 1 |
| GSM8056982 |
ATAC-seq: ARPE-19 HCMV-infected Replicate 2 |
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| This SubSeries is part of SuperSeries: |
| GSE254741 |
Human cytomegalovirus infection coopts chromatin organization to modulate TEAD1 transcription factor activity |
|
| Relations |
| BioProject |
PRJNA1071590 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE254734_ATAC_ARPE_HCMV.conservative_overlap.hg19.narrowPeak.gz |
5.4 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE254734_ATAC_ARPE_HCMV.pooled.hg19.bw |
262.3 Mb |
(ftp)(http) |
BW |
| GSE254734_ATAC_ARPE_HCMV_enriched.tsv.gz |
419.9 Kb |
(ftp)(http) |
TSV |
| GSE254734_ATAC_ARPE_UI.conservative_overlap.hg19.narrowPeak.gz |
6.4 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE254734_ATAC_ARPE_UI.pooled.hg19.bw |
309.1 Mb |
(ftp)(http) |
BW |
| GSE254734_ATAC_ARPE_UI_enriched.tsv.gz |
1.6 Mb |
(ftp)(http) |
TSV |
| GSE254734_ATAC_ARPE_shared.tsv.gz |
11.1 Mb |
(ftp)(http) |
TSV |
| GSE254734_ATAC_HS68_HCMV.conservative_overlap.hg19.narrowPeak.gz |
6.0 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE254734_ATAC_HS68_HCMV.pooled.hg19.bw |
264.1 Mb |
(ftp)(http) |
BW |
| GSE254734_ATAC_HS68_HCMV_enriched.tsv.gz |
3.3 Mb |
(ftp)(http) |
TSV |
| GSE254734_ATAC_HS68_UI.conservative_overlap.hg19.narrowPeak.gz |
6.2 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE254734_ATAC_HS68_UI.pooled.hg19.bw |
518.5 Mb |
(ftp)(http) |
BW |
| GSE254734_ATAC_HS68_UI_enriched.tsv.gz |
2.7 Mb |
(ftp)(http) |
TSV |
| GSE254734_ATAC_HS68_shared.tsv.gz |
9.5 Mb |
(ftp)(http) |
TSV |
| GSE254734_RAW.tar |
1.6 Gb |
(http)(custom) |
TAR (of BW, NARROWPEAK) |
SRA Run Selector |
| Raw data are available in SRA |
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