AP-1 subunits converge promiscuously at enhancers to potentiate transcription.

Journal Article (Journal Article)

The AP-1 transcription factor (TF) dimer contributes to many biological processes and environmental responses. AP-1 can be composed of many interchangeable subunits. Unambiguously determining the binding locations of these subunits in the human genome is challenging because of variable antibody specificity and affinity. Here, we definitively establish the genome-wide binding patterns of five AP-1 subunits by using CRISPR to introduce a common antibody tag on each subunit. We find limited evidence for strong dimerization preferences between subunits at steady state and find that, under a stimulus, dimerization patterns reflect changes in the transcriptome. Further, our analysis suggests that canonical AP-1 motifs indiscriminately recruit all AP-1 subunits to genomic sites, which we term AP-1 hotspots. We find that AP-1 hotspots are predictive of cell type-specific gene expression and of genomic responses to glucocorticoid signaling (more so than super-enhancers) and are significantly enriched in disease-associated genetic variants. Together, these results support a model where promiscuous binding of many AP-1 subunits to the same genomic location play a key role in regulating cell type-specific gene expression and environmental responses.

Full Text

Duke Authors

Cited Authors

  • Seo, J; Koçak, DD; Bartelt, LC; Williams, CA; Barrera, A; Gersbach, CA; Reddy, TE

Published Date

  • April 2021

Published In

Volume / Issue

  • 31 / 4

Start / End Page

  • 538 - 550

PubMed ID

  • 33674350

Pubmed Central ID

  • 33674350

Electronic International Standard Serial Number (EISSN)

  • 1549-5469

Digital Object Identifier (DOI)

  • 10.1101/gr.267898.120

Language

  • eng

Conference Location

  • United States