Accession	GSE254734
Status	2024/12/6
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.
Samples	GSM ID Sample info Characteristics Description GSM8056975 ATAC-seq: HS68 Uninfected Replicate 1 cell line: HS68;cell type: Foreskin fibroblast;infection: None - GSM8056976 ATAC-seq: HS68 Uninfected Replicate 2 cell line: HS68;cell type: Foreskin fibroblast;infection: None - GSM8056977 ATAC-seq: HS68 HCMV-infected Replicate 1 cell line: HS68;cell type: Foreskin fibroblast;infection: TB40/E HCMV - GSM8056978 ATAC-seq: HS68 HCMV-infected Replicate 2 cell line: HS68;cell type: Foreskin fibroblast;infection: TB40/E HCMV - GSM8056979 ATAC-seq: ARPE-19 Uninfected Replicate 1 cell line: ARPE-19;cell type: Retinal epithelial;infection: None - GSM8056980 ATAC-seq: ARPE-19 Uninfected Replicate 2 cell line: ARPE-19;cell type: Retinal epithelial;infection: None - GSM8056981 ATAC-seq: ARPE-19 HCMV-infected Replicate 1 cell line: ARPE-19;cell type: Retinal epithelial;infection: TB40/E HCMV - GSM8056982 ATAC-seq: ARPE-19 HCMV-infected Replicate 2 cell line: ARPE-19;cell type: Retinal epithelial;infection: TB40/E HCMV -
Platform	GPL24676  : Illumina NovaSeq 6000 (Homo sapiens)
Literature