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The SWI/SNF nucleosome remodeler constrains enhancer activity during Drosophila wing development
Matthew J Niederhuber1,2,3,4, Mary Leatham-Jensen2,3,4, Daniel J McKay2,3,4
1Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Genetics
|November 10, 2023
Summary
The BAP-specific subunit Osa constrains enhancer activity during development. Loss of Osa leads to hyperactivation of the Notch pathway and developmental defects, highlighting its role in regulating gene expression.
Area of Science:
- Developmental Biology
- Epigenetics
- Molecular Biology
Background:
- Chromatin remodeling regulates gene expression crucial for cell fate.
- Enhancer accessibility changes dynamically during development.
- Transcription factors and nucleosome remodelers collaborate to control enhancer accessibility.
Purpose of the Study:
- Investigate the role of nucleosome remodelers in dynamic enhancer activity control.
- Determine how short DNA stretches unmasked by factors yield large accessible regions.
- Understand the function of the BAP-specific subunit Osa in chromatin remodeling.
Main Methods:
- Genetic screen in Drosophila to identify key nucleosome remodelers.
- Genome-wide profiling to map Osa binding sites.
- Transgenic reporter analyses to assess enhancer activity.
Main Results:
- The BAP complex represses the dynamic enhancer brdisc.
- Osa is required for constraining brdisc activity, not for stage-specific accessibility changes.
- Osa binds thousands of developmentally dynamic regulatory sites, including Notch pathway genes.
- Osa loss causes Notch ligand Delta hyperactivation and ectopic sensory structure development.
Conclusions:
- Osa plays a critical role in constraining enhancer activity during development.
- Proper constraint of enhancer activity is essential for dose-dependent developmental events.
- Osa's function is vital for regulating the Notch signaling pathway and preventing developmental abnormalities.
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