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High-density P300 enhancers control cell state transitions.
Steven Witte1,2, Allan Bradley3, Anton J Enright4
1Integrative Immunobiology Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. steven.witte@nih.gov.
BMC Genomics
|November 8, 2015
Summary
Super-enhancers (SEs) marked by P300 identify key transcriptional control nodes during cell fate decisions. These SEs change during differentiation and activation, offering potential therapeutic targets for inflammatory diseases.
Area of Science:
- Molecular Biology
- Genomics
- Immunology
Background:
- Transcriptional enhancers regulate lineage-specific gene expression.
- Super-enhancers (SEs) are extended clusters of enhancers near key cell identity genes.
- SEs are enriched for disease-associated genetic variations, but P300 binding to SEs is poorly understood.
Purpose of the Study:
- To investigate the role of P300 in marking SEs.
- To explore SE function in cell fate decisions and immune responses.
- To identify potential therapeutic targets for inflammatory diseases.
Main Methods:
- ChIP-seq to identify P300 binding sites.
- Analysis of SEs in embryonic stem cells, T helper cells, and macrophages.
- Identification of expression quantitative trait loci (eQTL) in human monocytes.
Main Results:
- P300 marks a similar SE repertoire as Med1 and H3K27ac in embryonic stem cells.
- SEs play a role in mouse T helper cell fate decisions.
- SE-associated genes are upregulated during macrophage activation, and inflammatory SEs can be targeted.
Conclusions:
- P300-marked SEs identify key transcriptional control nodes in cell fate decisions.
- The SE landscape dynamically changes during cell differentiation and activation.
- SEs offer potential targets for treating inflammatory diseases.
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