AP-1 subunits converge promiscuously at enhancers to potentiate transcription.
Genome Res
; 31(4): 538-550, 2021 04.
Article
en En
| MEDLINE
| ID: mdl-33674350
ABSTRACT
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Transcripción Genética
/
Regulación de la Expresión Génica
/
Elementos de Facilitación Genéticos
/
Factor de Transcripción AP-1
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2021
Tipo del documento:
Article