TY - JOUR T1 - Diverse motif ensembles specify non-redundant DNA binding activities of AP-1 family members in macrophages JF - bioRxiv DO - 10.1101/345835 SP - 345835 AU - Gregory J. Fonseca AU - Jenhan Tao AU - Emma M. Westin AU - Sascha H. Duttke AU - Nathanael J. Spann AU - Tobias Strid AU - Zeyang Shen AU - Joshua D. Stender AU - Verena M. Link AU - Christopher Benner AU - Christopher K. Glass Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/06/13/345835.abstract N2 - Mechanisms by which members of the AP-1 family of transcription factors play both redundant and non-redundant biological roles despite recognizing the same DNA sequence remain poorly understood. To address this question, we investigated the molecular functions and genome-wide DNA binding patterns of AP-1 family members in macrophages. ChIP-sequencing showed overlapping and distinct binding profiles for each factor that were remodeled following TLR4 ligation. Development of a machine learning approach that jointly weighs hundreds of DNA recognition elements yielded dozens of motifs predicted to drive factor-specific binding profiles. Machine learning-based predictions were confirmed by analysis of the effects of mutations in genetically diverse mice and by loss of function experiments. These findings provide evidence that non-redundant genomic locations of different AP-1 family members in macrophages largely result from collaborative interactions with diverse, locus-specific ensembles of transcription factors and suggest a general mechanism for encoding functional specificities of their common recognition motif. ER -