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Integrative dissection of gene regulatory elements at base resolution
Zeyu Chen1,2,3, Nauman Javed1,2,3, Molly Moore2
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Cell Genomics
|June 30, 2023
Summary
Researchers identified critical DNA bases within a gene enhancer that control CD69 expression in T cells. Base editing revealed how these sequences regulate gene activity and cellular responses.
Area of Science:
- Genomics
- Immunology
- Molecular Biology
Background:
- Gene regulatory elements are numerous but their functional sequences are poorly understood.
- Dissecting regulatory elements in their native chromatin context is challenging.
Purpose of the Study:
- To identify specific sequence motifs and bases critical for enhancer function.
- To understand the regulatory mechanisms of CD69 induction in T cells.
Main Methods:
- Epigenetic perturbations
- Base editing
- Deep learning
- Analysis of the CD69 immune locus
Main Results:
- A ~170 base interval in a CD69 enhancer was identified as critical.
- Specific C-to-T base edits reduced enhancer accessibility, acetylation, and CD69 expression.
- Key transcription factors (GATA3, TAL1, BHLHE40) interactions were implicated.
Conclusions:
- The study provides a framework for dissecting regulatory elements in vivo.
- Interplay between GATA3 and BHLHE40 is crucial for rapid T cell responses.
- Identified functional variants can inform future research on gene regulation.
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