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Diverse motif ensem...
Diverse motif ensembles specify non-redundant DNA binding activities of AP-1 family members in macrophages.
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- Fonseca, Gregory J (author)
- Department of Cellular and Molecular Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USA
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- Tao, Jenhan (author)
- Department of Cellular and Molecular Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USA
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- Westin, Emma M (author)
- Department of Cellular and Molecular Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USA
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- Duttke, Sascha H (author)
- Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USA
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- Spann, Nathanael J (author)
- Department of Cellular and Molecular Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USA
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- Strid, Tobias (author)
- Department of Cellular and Molecular Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USA
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- Shen, Zeyang (author)
- Department of Bioengineering, Jacobs School of Engineering, University of California San Diego, La Jolla, CA, 92037, USA
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- Stender, Joshua D (author)
- Department of Cellular and Molecular Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USA
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- Sakai, Mashito (author)
- Department of Cellular and Molecular Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USA
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- Link, Verena M (author)
- Faculty of Biology, Division of Evolutionary Biology, Ludwig-Maximilian University of Munich, Munich, 80539, Germany
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- Benner, Christopher (author)
- Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USA
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- Glass, Christopher K (author)
- Department of Cellular and Molecular Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USA // Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USA
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(creator_code:org_t)
- 2019-01-24
- 2019
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Abstract
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- Mechanisms by which members of the AP-1 family of transcription factors play non-redundant biological roles despite recognizing the same DNA sequence remain poorly understood. To address this question, here we investigate the molecular functions and genome-wide DNA binding patterns of AP-1 family members in primary and immortalized mouse macrophages. ChIP-sequencing shows 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 yields dozens of motifs predicted to drive factor-specific binding profiles. Machine learning-based predictions are 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.
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- By the author/editor
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Fonseca, Gregory ...
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Tao, Jenhan
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Westin, Emma M
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Duttke, Sascha H
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Spann, Nathanael ...
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Strid, Tobias
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show more...
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Shen, Zeyang
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Stender, Joshua ...
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Sakai, Mashito
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Link, Verena M
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Benner, Christop ...
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Glass, Christoph ...
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- Articles in the publication
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Nature Communica ...
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Linköping University