Tissue-specific disallowance of housekeeping genes: The other face of cell differentiation
- Lieven Thorrez1,2,3,
- Ilaria Laudadio4,
- Katrijn Van Deun3,
- Roel Quintens1,3,
- Nico Hendrickx1,3,
- Mikaela Granvik1,3,
- Katleen Lemaire1,3,
- Anica Schraenen1,3,
- Leentje Van Lommel1,3,
- Stefan Lehnert1,3,
- Cristina Aguayo-Mazzucato5,
- Rui Cheng-Xue6,
- Patrick Gilon6,
- Iven Van Mechelen3,
- Susan Bonner-Weir5,
- Frédéric Lemaigre4 and
- Frans Schuit1,3,7
- 1 Gene Expression Unit, Department of Molecular Cell Biology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium;
- 2 ESAT-SCD, Department of Electrical Engineering, Katholieke Universiteit Leuven, 3000 Leuven, Belgium;
- 3 Center for Computational Systems Biology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium;
- 4 Université Catholique de Louvain, de Duve Institute, 1200 Brussels, Belgium;
- 5 Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard University, Boston, Massachusetts 02215, USA;
- 6 Unité d'Endocrinologie et Métabolisme, University of Louvain Faculty of Medicine, 1200 Brussels, Belgium
Abstract
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.
Footnotes
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↵7 Corresponding author.
E-mail frans.schuit{at}med.kuleuven.be; fax 32-16-345995.
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[Supplemental material is available online at http://www.genome.org. The microarray data have been submitted to the NCBI Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/) under accession nos. GSE24207 and GSE24940.]
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Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.109173.110.
- Received April 19, 2010.
- Accepted November 9, 2010.
- Copyright © 2011 by Cold Spring Harbor Laboratory Press
Freely available online through the Genome Research Open Access option.