A cofactor-induced repressive type of transcription factor condensation can be induced by synthetic peptides to suppress tumorigenesis

ABSTRACT: Transcriptional factors (TFs) act as key determinants of cell death and survival by differentially modulating gene expression. Here, we identified many TFs, including TEAD4, that form condensates in stressed cells. In contrast to YAP-induced transcription-activating condensates of TEAD4, we found that co-factors such as VGLL4 and RFXANK alternatively induced repressive TEAD4 condensates to trigger cell death upon glucose starvation. Focusing on VGLL4, we demonstrated that heterotypic interactions between TEAD4 and VGLL4 favor the oligomerization and assembly of large TEAD4 condensates with a nonclassical inhibitory function, i.e., causing DNA/chromatin to be aggregated and entangled, which eventually impede gene expression. Based on these findings, we engineered a peptide derived from the

SUBMITTER: Prof. Zhaocai Zhou 

PROVIDER: S-SCDT-10_1038-S44318-024-00257-4 | biostudies-other |

REPOSITORIES: biostudies-other