SWI/SNF complex-mediated ZNF410 cooperative binding maintains chromatin accessibility and enhancer activity

• DOI: 10.1016/j.celrep.2025.115476
• Publication Date: 2025-04-01T02:14:45Z
• Authors: Siyuan Xu; Chuxuan Peng; Ren Ren; Haowen Lu; Han Zhao; Sijian Xia; Yijie Shen; Bin Xu; Haoyue Zhang; Xiaodong Cheng; Gerd A. Blobel; Xianjiang Lan
• Keywords: SWI/SNF

Highlights•ZNF410 maintains the accessibility of CHD4 enhancer regions•ZNF410 binds to homotypic clustered motifs in a cooperative manner•SWI/SNF complex is selectively required mediate ZNF410 binding•The N terminus enables recruitment SWI/SNF complexSummaryThe clustering multiple transcription factor binding sites (TFBSs) for same TF has proved be pervasive feature cis-regulatory elements eukaryotic genome. However, contribution within clusters TFBSs (HCTs) and target gene expression remains understood. Here, we characterize enhancers that harbor unique functional HCTs genome wide. We uncover controls chromatin activity regions. demonstrate collaborative fashion, further conferring transcriptional activation. In particular, three (sub-HCTs) located at 3′ end distal act as "switch motifs" control activity. Mechanistically, expression. Together, our findings expose hierarchy motifs, which cooperate fine-tune expression.Graphical abstract