Enhancer selectivity across cell types delineates three functionally distinct enhancer-promoter regulation patterns.
Enhancer selectivity
Enhancer-promoter interactions
Gene regulation patterns across cell types
Journal
BMC genomics
ISSN: 1471-2164
Titre abrégé: BMC Genomics
Pays: England
ID NLM: 100965258
Informations de publication
Date de publication:
16 May 2024
16 May 2024
Historique:
received:
31
01
2024
accepted:
13
05
2024
medline:
16
5
2024
pubmed:
16
5
2024
entrez:
15
5
2024
Statut:
epublish
Résumé
Multiple enhancers co-regulating the same gene is prevalent and plays a crucial role during development and disease. However, how multiple enhancers coordinate the same gene expression across various cell types remains largely unexplored at genome scale. We develop a computational approach that enables the quantitative assessment of enhancer specificity and selectivity across diverse cell types, leveraging enhancer-promoter (E-P) interactions data. We observe two well-known gene regulation patterns controlled by enhancer clusters, which regulate the same gene either in a limited number of cell types (Specific pattern, Spe) or in the majority of cell types (Conserved pattern, Con), both of which are enriched for super-enhancers (SEs). We identify a previously overlooked pattern (Variable pattern, Var) that multiple enhancers link to the same gene, but rarely coexist in the same cell type. These three patterns control the genes associating with distinct biological function and exhibit unique epigenetic features. Specifically, we discover a subset of Var patterns contains Shared enhancers with stable enhancer-promoter interactions in the majority of cell types, which might contribute to maintaining gene expression by recruiting abundant CTCF. Together, our findings reveal three distinct E-P regulation patterns across different cell types, providing insights into deciphering the complexity of gene transcriptional regulation.
Sections du résumé
BACKGROUND
BACKGROUND
Multiple enhancers co-regulating the same gene is prevalent and plays a crucial role during development and disease. However, how multiple enhancers coordinate the same gene expression across various cell types remains largely unexplored at genome scale.
RESULTS
RESULTS
We develop a computational approach that enables the quantitative assessment of enhancer specificity and selectivity across diverse cell types, leveraging enhancer-promoter (E-P) interactions data. We observe two well-known gene regulation patterns controlled by enhancer clusters, which regulate the same gene either in a limited number of cell types (Specific pattern, Spe) or in the majority of cell types (Conserved pattern, Con), both of which are enriched for super-enhancers (SEs). We identify a previously overlooked pattern (Variable pattern, Var) that multiple enhancers link to the same gene, but rarely coexist in the same cell type. These three patterns control the genes associating with distinct biological function and exhibit unique epigenetic features. Specifically, we discover a subset of Var patterns contains Shared enhancers with stable enhancer-promoter interactions in the majority of cell types, which might contribute to maintaining gene expression by recruiting abundant CTCF.
CONCLUSIONS
CONCLUSIONS
Together, our findings reveal three distinct E-P regulation patterns across different cell types, providing insights into deciphering the complexity of gene transcriptional regulation.
Identifiants
pubmed: 38750461
doi: 10.1186/s12864-024-10408-w
pii: 10.1186/s12864-024-10408-w
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
483Subventions
Organisme : National Natural Science Foundation of China
ID : 32070635
Organisme : Fundamental Research Funds for the Central Universities
ID : 20720230068
Informations de copyright
© 2024. The Author(s).
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