Accession	GSE254736
Status	2024/12/6
Title	Human cytomegalovirus infection coopts chromatin organization to modulate TEAD1 transcription factor activity [ChIP-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 GSM8056987 H3K27ac ChIP-seq: HS68 Uninfected Replicate 1 cell line: HS68;cell type: Foreskin fibroblast;infection: None;chip antibody: Abcam ab4729, lot GR3357415-1 - GSM8056988 H3K27ac ChIP-seq: HS68 Uninfected Replicate 2 cell line: HS68;cell type: Foreskin fibroblast;infection: None;chip antibody: Abcam ab4729, lot GR3357415-1 - GSM8056989 H3K27ac ChIP-seq: HS68 HCMV-infected Replicate 1 cell line: HS68;cell type: Foreskin fibroblast;infection: TB40/E HCMV;chip antibody: Abcam ab4729, lot GR3357415-1 - GSM8056990 H3K27ac ChIP-seq: HS68 HCMV-infected Replicate 2 cell line: HS68;cell type: Foreskin fibroblast;infection: TB40/E HCMV;chip antibody: Abcam ab4729, lot GR3357415-1 - GSM8056991 CTCF ChIP-seq: HS68 Uninfected Replicate 1 cell line: HS68;cell type: Foreskin fibroblast;infection: None;chip antibody: ActiveMotif 61311, lot 17118005 - GSM8056992 CTCF ChIP-seq: HS68 Uninfected Replicate 2 cell line: HS68;cell type: Foreskin fibroblast;infection: None;chip antibody: ActiveMotif 61311, lot 17118005 - GSM8056993 CTCF ChIP-seq: HS68 HCMV-infected Replicate 1 cell line: HS68;cell type: Foreskin fibroblast;infection: TB40/E HCMV;chip antibody: ActiveMotif 61311, lot 17118005 - GSM8056994 CTCF ChIP-seq: HS68 HCMV-infected Replicate 2 cell line: HS68;cell type: Foreskin fibroblast;infection: TB40/E HCMV;chip antibody: ActiveMotif 61311, lot 17118005 - GSM8056995 TEAD1 ChIP-seq: HS68 Uninfected Replicate 1 cell line: HS68;cell type: Foreskin fibroblast;infection: None;chip antibody: ActiveMotif 61643, lot 34614001 - GSM8056996 TEAD1 ChIP-seq: HS68 Uninfected Replicate 2 cell line: HS68;cell type: Foreskin fibroblast;infection: None;chip antibody: ActiveMotif 61643, lot 34614001 - GSM8056997 TEAD1 ChIP-seq: HS68 HCMV-infected Replicate 1 cell line: HS68;cell type: Foreskin fibroblast;infection: TB40/E HCMV;chip antibody: ActiveMotif 61643, lot 34614001 - GSM8056998 TEAD1 ChIP-seq: HS68 HCMV-infected Replicate 2 cell line: HS68;cell type: Foreskin fibroblast;infection: TB40/E HCMV;chip antibody: ActiveMotif 61643, lot 34614001 -
Platform	GPL24676  : Illumina NovaSeq 6000 (Homo sapiens)
Literature