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An E box comprises a positional sensor for regional differences in skeletal muscle gene expression and methylation
E Ceccarelli1, M J McGrew, T Nguyen
1Cardiovascular Research Center, Massachusetts General Hospital-East, Charlestown, Massachusetts 02129, USA.
Developmental Biology
|August 24, 1999
Summary
A specific DNA sequence (E box) in skeletal muscle genes acts as a positional sensor. Its interaction with proteins like Hox regulates gene expression, ensuring correct muscle development and function.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- Skeletal muscle gene expression patterns are positionally restricted, providing positional information.
- Regulatory sequences from the MLC1/3 locus drive graded transgene expression in segmented axial muscles.
Purpose of the Study:
- To identify molecular mechanisms controlling positional information in skeletal muscles.
- To characterize regulatory elements responsible for positionally restricted gene expression.
Main Methods:
- Characterization of control elements using a muscle-specific transgene reporter.
- Mutation of a conserved E box within the MLC enhancer core.
- Analysis of transgene expression in transfected muscle cells and transgenic mice.
- Assessment of DNA methylation patterns.
Main Results:
- A conserved E box in the MLC enhancer is targeted by a nuclear protein complex including Hox proteins.
- Mutation of this E box in transgenic mice released rostral restriction of transgene expression.
- Increased transgene activity correlated with reduced DNA methylation in the promoter and enhancer regions.
Conclusions:
- An E box and its associated proteins function as a positional sensor in axial skeletal muscle gene expression.
- This mechanism is crucial for establishing regional differences in gene expression and accessibility.
- Identifies a novel role for E box-binding proteins in developmental positional signaling.