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Genome-wide binding potential and regulatory activity of the glucocorticoid receptor’s monomeric and dimeric forms

Author

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  • Thomas A. Johnson

    (Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH)

  • Ville Paakinaho

    (Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH
    University of Eastern Finland, Kuopio)

  • Sohyoung Kim

    (Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH)

  • Gordon L. Hager

    (Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH)

  • Diego M. Presman

    (Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH
    Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales)

Abstract

A widely regarded model for glucocorticoid receptor (GR) action postulates that dimeric binding to DNA regulates unfavorable metabolic pathways while monomeric receptor binding promotes repressive gene responses related to its anti-inflammatory effects. This model has been built upon the characterization of the GRdim mutant, reported to be incapable of DNA binding and dimerization. Although quantitative live-cell imaging data shows GRdim as mostly dimeric, genomic studies based on recovery of enriched half-site response elements suggest monomeric engagement on DNA. Here, we perform genome-wide studies on GRdim and a constitutively monomeric mutant. Our results show that impairing dimerization affects binding even to open chromatin. We also find that GRdim does not exclusively bind half-response elements. Our results do not support a physiological role for monomeric GR and are consistent with a common mode of receptor binding via higher order structures that drives both the activating and repressive actions of glucocorticoids.

Suggested Citation

  • Thomas A. Johnson & Ville Paakinaho & Sohyoung Kim & Gordon L. Hager & Diego M. Presman, 2021. "Genome-wide binding potential and regulatory activity of the glucocorticoid receptor’s monomeric and dimeric forms," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22234-9
    DOI: 10.1038/s41467-021-22234-9
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