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Reduced levels of t...
Reduced levels of two modifiers of epigenetic gene silencing, Dnmt3a and Trim28, cause increased phenotypic noise
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- Whitelaw, Nadia C (author)
- Queensland Institute of Medical Research, Brisbane, Australia
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- Chong, Suyinn (author)
- Queensland Institute of Medical Research, Brisbane, Australia
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- Morgan, Daniel K (author)
- Queensland Institute of Medical Research, Brisbane, Australia
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- Nestor, Colm, 1977- (author)
- University of Edinburgh, UK
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- Bruxner, Timothy J (author)
- Queensland Institute of Medical Research, Brisbane, Australia
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- Ashe, Alyson (author)
- Queensland Institute of Medical Research, Brisbane, Australia
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- Lambley, Eleanore (author)
- Queensland Institute of Medical Research, Brisbane, Australia
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- Meehan, Richard (author)
- Institute of Genetics and Molecular Medicine, Edinburgh, UK
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- Whitelaw, Emma (author)
- University of Edinburgh, UK
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(creator_code:org_t)
- 2010-11-19
- 2010
- English.
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In: Genome Biology. - : BioMed Central. - 1465-6906 .- 1474-760X. ; 11:11
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Abstract
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- BACKGROUND: Inbred individuals reared in controlled environments display considerable variance in many complex traits but the underlying cause of this intangible variation has been an enigma. Here we show that two modifiers of epigenetic gene silencing play a critical role in the process.RESULTS: Inbred mice heterozygous for a null mutation in DNA methyltransferase 3a (Dnmt3a) or tripartite motif protein 28 (Trim28) show greater coefficients of variance in body weight than their wild-type littermates. Trim28 mutants additionally develop metabolic syndrome and abnormal behavior with incomplete penetrance. Genome-wide gene expression analyses identified 284 significantly dysregulated genes in Trim28 heterozygote mutants compared to wild-type mice, with Mas1, which encodes a G-protein coupled receptor implicated in lipid metabolism, showing the greatest average change in expression (7.8-fold higher in mutants). This gene also showed highly variable expression between mutant individuals.CONCLUSIONS: These studies provide a molecular explanation of developmental noise in whole organisms and suggest that faithful epigenetic control of transcription is central to suppressing deleterious levels of phenotypic variation. These findings have broad implications for understanding the mechanisms underlying sporadic and complex disease in humans.
Subject headings
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Whitelaw, Nadia ...
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Chong, Suyinn
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Morgan, Daniel K
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Nestor, Colm, 19 ...
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Bruxner, Timothy ...
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Ashe, Alyson
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show more...
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Lambley, Eleanor ...
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Meehan, Richard
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Whitelaw, Emma
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
- Articles in the publication
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Genome Biology
- By the university
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Linköping University