2026-10-12T09:16:53Z https://data.mendeley.com/oai

oai:data.mendeley.com/x6z25n3z2z.1 2024-06-17T10:05:38Z

Godin, Holly Systematic Dissection of Sequence Features Affecting the Binding Specificity of a Pioneer Factor Reveals Binding Synergy Between FOXA1 and AP-1 Mendeley Data Despite the unique ability of pioneer transcription factors (PFs) to target nucleosomal sites in closed chromatin, they only bind a small fraction of their genomic motifs. The underlying mechanism of this selectivity is not well understood. Here, we design a high-throughput assay called ChIP-ISO to systematically dissect sequence features affecting the binding specificity of a classic PF, FOXA1, in human A549 cells. Combining ChIP-ISO with in vitro and neural network analyses, we find that 1) FOXA1 binding is strongly affected by co-binding TFs AP-1 and CEBPB, 2) FOXA1 and AP-1 show binding cooperativity in vitro, 3) FOXA1’s binding is determined more by local sequences than chromatin context, including eu-/heterochromatin, and 4) AP-1 is partially responsible for differential binding of FOXA1 in different cell types. Our study presents a framework for elucidating genetic rules underlying PF binding specificity and reveals a mechanism for context-specific regulation of its binding. Synthetic Biology Transcription Factor Gene Regulation Xu, Cheng Yang, Jianyu Leith, Erik Johnson, Jenna Tan, Song Mahony, Shaun Bai, Lu Dataset doi:10.17632/x6z25n3z2z.1 oai:data.mendeley.com/x6z25n3z2z.1 Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0 https://data.mendeley.com/datasets/x6z25n3z2z 2024-06-17T10:05:38Z