title: Tissue-specific disallowance of housekeeping genes: the other face of cell differentiation.
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.
authors.affiliation: Gene Expression Unit, Department of Molecular Cell Biology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
authors.forename: Lieven
authors.initials: L
authors.lastname: Thorrez
authors.forename: Ilaria
authors.initials: I
authors.lastname: Laudadio
authors.forename: Katrijn
authors.initials: K
authors.lastname: Van Deun
authors.forename: Roel
authors.initials: R
authors.lastname: Quintens
authors.forename: Nico
authors.initials: N
authors.lastname: Hendrickx
authors.forename: Mikaela
authors.initials: M
authors.lastname: Granvik
authors.forename: Katleen
authors.initials: K
authors.lastname: Lemaire
authors.forename: Anica
authors.initials: A
authors.lastname: Schraenen
authors.forename: Leentje
authors.initials: L
authors.lastname: Van Lommel
authors.forename: Stefan
authors.initials: S
authors.lastname: Lehnert
authors.forename: Cristina
authors.initials: C
authors.lastname: Aguayo-Mazzucato
authors.forename: Rui
authors.initials: R
authors.lastname: Cheng-Xue
authors.forename: Patrick
authors.initials: P
authors.lastname: Gilon
authors.forename: Iven
authors.initials: I
authors.lastname: Van Mechelen
authors.forename: Susan
authors.initials: S
authors.lastname: Bonner-Weir
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lemaigre
authors.forename: Frans
authors.initials: F
authors.lastname: Schuit
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D057890:Epigenomics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D045022:Lactate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D045022:Lactate Dehydrogenases; D035683:MicroRNAs; D027501:Monocarboxylic Acid Transporters; D012333:RNA, Messenger; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C071195:D-lactate dehydrogenase