biostudies-literatureSayeed KBLRD VANIDCR NIH HHSNIAID NIH HHSNIEHS NIH HHSNHGRI NIH HHSNINDS NIH HHSNIAMS NIH HHSNIH HHSNIGMS NIH HHSRP101578https://www.ebi.ac.uk/biostudies/studies/S-EPMC12422734biostudies-literatureUnknown13Human cytomegalovirus (HCMV) infects up to 80% of the world's population. Here, we show that HCMV infection leads to widespread changes in human chromatin accessibility and chromatin looping, with hundreds of thousands of genomic regions affected 48 hr after infection. Integrative analyses reveal HCMV-induced perturbation of Hippo signaling through drastic reduction of TEAD1 transcription factor activity. We confirm extensive concordant loss of TEAD1 binding, active H3K27ac histone marks, and chromatin looping interactions upon infection. Our data position TEAD1 at the top of a hierarchy involving multiple altered important developmental pathways. HCMV infection reduces TEAD1 activity through four distinct mechanisms: closing of TEAD1-bound chromatin, reduction of YAP1 and phosphorylated YeLifeHuman cytomegalovirus infection coopts chromatin organization to diminish TEAD1 transcription factor activity.PMC12422734R21 DE026267R01 AI164709I01 BX001834T32 AI007245F32 AI172329U01 AI130830P30 AR070549T32 ES007250I01 BX003850R01 HG010730U19 AI070235R01 AI121028R01 NS099068I01 BX006254R01 AI024717R01 AR073228R01 GM055479R01 AI148276U01 HG011172Richards SGewurz BEBeucler MJYechoor VZhao BMiller WEWeirauch MTDunn KACrowther AForney CRParameswaran SKaufman KMLeong MMLEdsall LEHesse HKSayeed KDonmez OAHarley JBVonHandorf AWright JKottyan LCHass MRJones SHMurray-Nerger LAfalseHuman cytomegalovirus infection coopts chromatin organization to diminish TEAD1 transcription factor activity.Human cytomegalovirus (HCMV) infects up to 80% of the world's population. Here, we show that HCMV infection leads to widespread changes in human chromatin accessibility and chromatin looping, with hundreds of thousands of genomic regions affected 48 hr after infection. Integrative analyses reveal HCMV-induced perturbation of Hippo signaling through drastic reduction of TEAD1 transcription factor activity. We confirm extensive concordant loss of TEAD1 binding, active H3K27ac histone marks, and chromatin looping interactions upon infection. Our data position TEAD1 at the top of a hierarchy involving multiple altered important developmental pathways. HCMV infection reduces TEAD1 activity through four distinct mechanisms: closing of TEAD1-bound chromatin, reduction of YAP1 and phosphorylated Y2025-01-01T00:00:00Z2025 Sep2026-06-02T20:27:11.725Z2026-04-20T03:10:18.224ZS-EPMC124227344092834710.7554/eLife.101578