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Comparative Analysis of Immune Cells Reveals a Conserved Regulatory Lexicon
Elisa Donnard1, Pranitha Vangala1, Shaked Afik2
1Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Cell Systems
|February 19, 2018
Summary
Most gene enhancers are not conserved, but conserved enhancers are crucial for strongly induced genes in the innate immune system. Motif instances predict gene responsiveness to pathogen detection.
Area of Science:
- Genomics
- Molecular Biology
- Immunology
Background:
- Most well-studied enhancers are highly conserved across species.
- Previous studies indicated limited conservation of active enhancers in steady-state systems.
Purpose of the Study:
- To investigate the conservation of enhancer activity using a comparative genomics approach.
- To integrate temporal expression and epigenetic profiles within an innate immune system context.
Main Methods:
- Comparative genomics analysis.
- Integration of temporal gene expression and epigenetic profiles.
- Clustering of conserved accessible DNA sequences to identify sequence motifs.
Main Results:
- Gene expression programs diverge for mildly induced genes but are highly conserved for strongly induced genes.
- A higher fraction of conserved enhancers regulates induced and early-response genes.
- Over 60 sequence motifs were identified, including known and novel factors.
- The number of motif instances strongly predicts gene responsiveness to pathogen detection.
Conclusions:
- Enhancer conservation is context-dependent, particularly within innate immune responses.
- Conserved sequence motifs within enhancers play a key role in regulating gene inducibility and pathogen response.
- This study provides insights into the evolutionary dynamics of gene regulation.
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