biostudies-literatureBejjani FCancéropôle Grand OuestLigue Contre le Cancer129https://www.ebi.ac.uk/biostudies/studies/S-EPMC10354941biostudies-literatureUnknown13(1)<h4>Background</h4>How transcription factors (TFs) down-regulate gene expression remains ill-understood, especially when they bind to multiple enhancers contacting the same gene promoter. In particular, it is not known whether they exert similar or significantly different molecular effects at these enhancers.<h4>Results</h4>To address this issue, we used a particularly well-suited study model consisting of the down-regulation of the TGFB2 gene by the TF Fra-1 in Fra-1-overexpressing cancer cells, as Fra-1 binds to multiple enhancers interacting with the TGFB2 promoter. We show that Fra-1 does not repress TGFB2 transcription via reducing RNA Pol II recruitment at the gene promoter but by decreasing the formation of its transcription-initiating form. This is associated with complex long-rangCell & bioscienceMultiple Fra-1-bound enhancers showing different molecular and functional features can cooperate to repress gene transcription.PMC103549411923762017-E08Equipe Labellisée EL2019Piechaczyk MBejjani FJariel-Encontre IZibara KTolza CEvanno EMahfoud SfalseMultiple Fra-1-bound enhancers showing different molecular and functional features can cooperate to repress gene transcription.<h4>Background</h4>How transcription factors (TFs) down-regulate gene expression remains ill-understood, especially when they bind to multiple enhancers contacting the same gene promoter. In particular, it is not known whether they exert similar or significantly different molecular effects at these enhancers.<h4>Results</h4>To address this issue, we used a particularly well-suited study model consisting of the down-regulation of the TGFB2 gene by the TF Fra-1 in Fra-1-overexpressing cancer cells, as Fra-1 binds to multiple enhancers interacting with the TGFB2 promoter. We show that Fra-1 does not repress TGFB2 transcription via reducing RNA Pol II recruitment at the gene promoter but by decreasing the formation of its transcription-initiating form. This is associated with complex long-rang2023-01-01T00:00:00Z2023 Jul2025-07-02T03:04:48.991Z2025-07-02T03:04:48.991ZS-EPMC103549413746438010.1186/s13578-023-01077-5