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  • Rewiring of the promoter-enhancer interactome and regulatory landscape in glioblastoma orchestrates gene expression underlying neurogliomal synaptic communication.

Rewiring of the promoter-enhancer interactome and regulatory landscape in glioblastoma orchestrates gene expression underlying neurogliomal synaptic communication.

Nature communications (2023-10-14)
Chaitali Chakraborty, Itzel Nissen, Craig A Vincent, Anna-Carin Hägglund, Andreas Hörnblad, Silvia Remeseiro
RÉSUMÉ

Chromatin organization controls transcription by modulating 3D-interactions between enhancers and promoters in the nucleus. Alterations in epigenetic states and 3D-chromatin organization result in gene expression changes contributing to cancer. Here, we map the promoter-enhancer interactome and regulatory landscape of glioblastoma, the most aggressive primary brain tumour. Our data reveals profound rewiring of promoter-enhancer interactions, chromatin accessibility and redistribution of histone marks in glioblastoma. This leads to loss of long-range regulatory interactions and overall activation of promoters, which orchestrate changes in the expression of genes associated to glutamatergic synapses, axon guidance, axonogenesis and chromatin remodelling. SMAD3 and PITX1 emerge as major transcription factors controlling genes related to synapse organization and axon guidance. Inhibition of SMAD3 and neuronal activity stimulation cooperate to promote proliferation of glioblastoma cells in co-culture with glutamatergic neurons, and in mice bearing patient-derived xenografts. Our findings provide mechanistic insight into the regulatory networks that mediate neurogliomal synaptic communication.

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A 83-01, ≥98% (HPLC)
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Sigma-Aldrich
Smad3 Inhibitor, SIS3, Smad3 Inhibitor, SIS3, CAS 1009104-85-1, is a cell-permeable, selective inhibitor of TGF-β1-dependent Smad3 phosphorylation and Smad3-mediated signaling. Does not affect Smad2, MAPK, ERK, or PI3-K.
Se connecterpour consulter vos tarifs contractuels et ceux de votre entreprise/organisme
RéférenceConditionnementDisponibilitéPrixQuantité
5 ea
Veuillez contacter notre Service Clients pour connaître la disponibilité de ce produit.
538,00 €
1 ea
Veuillez contacter notre Service Clients pour connaître la disponibilité de ce produit.
664,00 €