biostudies-literatureUnknownNicoletti CNIAMS NIH HHSNIH HHSNIGMS NIH HHSMYOD is an E-box sequence-specific basic Helix-Loop-Helix (bHLH) transcriptional activator that, when expressed in non-muscle cells, induces nuclear reprogramming toward skeletal myogenesis by promoting chromatin accessibility at previously silent loci. Here, we report on the identification of a previously unrecognized property of MYOD as repressor of gene expression, via E-box-independent chromatin binding within accessible genomic elements, which invariably leads to reduced chromatin accessibility. MYOD-mediated repression requires the integrity of functional domains previously implicated in MYOD-mediated activation of gene expression. Repression of mitogen- and growth factor-responsive genes occurs through promoter binding and requires a highly conserved domain within the first helix. RbioRxiv : the preprint server for biology2024.12.05.627024https://www.ebi.ac.uk/biostudies/studies/S-EPMC11643108biostudies-literatureE-box independent chromatin recruitment turns MYOD into a transcriptional repressor.PMC11643108R01 GM134712S10 OD026929R01 AR056712R01 GM137117R01 AR045203Nicolau MSundar SXu MMassenet JPintado-Urbanc APZhang WPuri PLConnor LJFang ZNicoletti CChan TCITapscott SJCheung THCaputo LSchmitt ASimon MDfalseE-box independent chromatin recruitment turns MYOD into a transcriptional repressor.MYOD is an E-box sequence-specific basic Helix-Loop-Helix (bHLH) transcriptional activator that, when expressed in non-muscle cells, induces nuclear reprogramming toward skeletal myogenesis by promoting chromatin accessibility at previously silent loci. Here, we report on the identification of a previously unrecognized property of MYOD as repressor of gene expression, via E-box-independent chromatin binding within accessible genomic elements, which invariably leads to reduced chromatin accessibility. MYOD-mediated repression requires the integrity of functional domains previously implicated in MYOD-mediated activation of gene expression. Repression of mitogen- and growth factor-responsive genes occurs through promoter binding and requires a highly conserved domain within the first helix. R2024-01-01T00:00:00Z2024 Dec2026-04-08T18:47:09.771Z2025-04-06T22:28:24.471ZS-EPMC116431083967779610.1101/2024.12.05.627024