Journal
GENOME RESEARCH
Volume 21, Issue 1, Pages 95-105Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.109173.110
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Funding
- K.U. Leuven [GOA/2004/11, GOA/2005/04, GOA/2009/10, CoE EF/05/007]
- Fonds voor Wetenschappelijk Onderzoek Vlaanderen (FWO) [G.0733.09N]
- Belgian Science Policy [PAI 6/20, 6/40]
- D.G. Higher Education and Scientific Research of the French Community of Belgium
- Juvenile Diabetes Research Foundation (JDRF) [2006-182, 2007-685]
- National Institutes of Health (NIH) [NIH R01 DK 66056]
- Televie (Belgium)
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK066056, R01DK093909] Funding Source: NIH RePORTER
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We report on a hitherto poorly characterized class of genes that are expressed in all tissues, except in one. Often, these genes have been classified as housekeeping genes, based on their nearly ubiquitous expression. However, the specific repression in one tissue defines a special class of disallowed genes.'' In this paper, we used the intersection-union test to screen for such genes in a multi-tissue panel of genome-wide mRNA expression data. We propose that disallowed genes need to be repressed in the specific target tissue to ensure correct tissue function. We provide mechanistic data of repression with two metabolic examples, exercise-induced inappropriate insulin release and interference with ketogenesis in liver. Developmentally, this repression is established during tissue maturation in the early postnatal period involving epigenetic changes in histone methylation. In addition, tissue-specific expression of microRNAs can further diminish these repressed mRNAs. Together, we provide a systematic analysis of tissue-specific repression of housekeeping genes, a phenomenon that has not been studied so far on a genome-wide basis and, when perturbed, can lead to human disease.
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