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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
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Epigenetic control of transgene expression and imprinting by genotype-specific modifiers
N D Allen1, M L Norris, M A Surani
1Department of Molecular Embryology, AFRC Institute of Animal Physiology and Genetics Research, Babraham, Cambridge, England.
Cell
|June 1, 1990
Summary
Genotype-specific modifier genes control transgene expression and DNA methylation. Epigenetic modifications at the TKZ751 locus can become irreversible in mice, impacting gene penetrance and imprinting.
Area of Science:
- Genetics
- Epigenetics
- Molecular Biology
Background:
- The regulation of transgene expression and DNA methylation is crucial for understanding gene control.
- Genetic backgrounds can influence epigenetic modifications and gene expression patterns.
Purpose of the Study:
- To investigate the role of genotype-specific modifier genes in controlling the expression and DNA methylation of the TKZ751 transgene locus.
- To determine the impact of different genetic backgrounds (DBA/2, 129, BALB/c) on transgene epigenetic modifications.
- To examine the inheritance patterns and reversibility of epigenetic modifications across generations.
Main Methods:
- Analysis of transgene locus TKZ751 expression and DNA methylation across different mouse genetic backgrounds.
- Investigating maternal inheritance effects of the BALB/c genetic background.
- Tracking epigenetic modifications over successive generations.
Main Results:
- DBA/2 and 129 genetic backgrounds enhanced TKZ751 expression.
- BALB/c background suppressed expression, particularly with maternal inheritance.
- Epigenetic modifications were cumulative and became irreversible in BALB/c mice after three germline passages.
- The germline failed to reverse previously acquired epigenetic modifications at the TKZ751 locus.
Conclusions:
- Genotype-specific modifier genes regulate penetrance and expressivity of the TKZ751 locus.
- Epigenetic modifications, including DNA methylation, play a key role in this regulation.
- The study highlights a failure in germline epigenetic reprogramming at the TKZ751 locus in specific genetic contexts, affecting parental imprinting.
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