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  • Fonseca, Gregory JDepartment of Cellular and Molecular Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USA (author)

Diverse motif ensembles specify non-redundant DNA binding activities of AP-1 family members in macrophages.

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2019-01-24
  • Springer Science and Business Media LLC,2019
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:liu-154612
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-154612URI
  • https://doi.org/10.1038/s41467-018-08236-0DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

Added entries (persons, corporate bodies, meetings, titles ...)

  • Tao, JenhanDepartment of Cellular and Molecular Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USA(Swepub:liu)n / a (author)
  • Westin, Emma MDepartment of Cellular and Molecular Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USA(Swepub:liu)n / a (author)
  • Duttke, Sascha HDepartment of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USA(Swepub:liu)n / a (author)
  • Spann, Nathanael JDepartment of Cellular and Molecular Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USA(Swepub:liu)n / a (author)
  • Strid, TobiasDepartment of Cellular and Molecular Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USA(Swepub:liu)tobst76 (author)
  • Shen, ZeyangDepartment of Bioengineering, Jacobs School of Engineering, University of California San Diego, La Jolla, CA, 92037, USA(Swepub:liu)n / a (author)
  • Stender, Joshua DDepartment of Cellular and Molecular Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USA(Swepub:liu)n / a (author)
  • Sakai, MashitoDepartment of Cellular and Molecular Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USA(Swepub:liu)n / a (author)
  • Link, Verena MFaculty of Biology, Division of Evolutionary Biology, Ludwig-Maximilian University of Munich, Munich, 80539, Germany(Swepub:liu)n / a (author)
  • Benner, ChristopherDepartment of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USA(Swepub:liu)n / a (author)
  • Glass, Christopher KDepartment 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(Swepub:liu)n / a (author)
  • Department of Cellular and Molecular Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USADepartment of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USA (creator_code:org_t)

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  • In:Nature Communications: Springer Science and Business Media LLC10:12041-1723

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