Transcriptional compensation for loss of an allele of the Ini1 tumor suppressor
Student Authors
Cynthia J. GuidiUMass Chan Affiliations
Department of Cell BiologyDocument Type
Journal ArticlePublication Date
2004-02-06Keywords
Alleles; Animals; Base Sequence; Cells, Cultured; Chromosomal Proteins, Non-Histone; DNA-Binding Proteins; *Genes, Tumor Suppressor; Heterozygote; Mice; Mice, Mutant Strains; Neoplasms, Experimental; Promoter Regions (Genetics); RNA, Messenger; Transcription, GeneticCell Biology
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
The gene encoding INI1, a component of the mammalian SWI/SNF ATP-dependent chromatin remodeling enzymes, has been classified as a tumor suppressor in humans. Gene-targeting experiments confirmed that Ini1 also functions as a tumor suppressor in mice. Although Ini1-null mice are embryonic lethal, 15-30% of mice heterozygous for Ini1 presented with poorly differentiated tumors with variable rhabdoid features. All tumors examined showed loss of heterozygosity at the Ini1 locus. We report here that cells and tissues heterozygous for the Ini1 tumor suppressor express levels of Ini1 protein and message roughly equivalent to the levels observed in wild type counterparts. Compensation of Ini1 is mediated by an increase in the rate of transcription from the Ini1 promoter. Moreover, when Ini1 is expressed exogenously, transcription from the endogenous promoter is reduced, suggesting that Ini1 levels are tightly regulated. This is the first report describing transcriptional compensation for haploinsufficiency of a tumor suppressor gene.Source
J Biol Chem. 2004 Feb 6;279(6):4180-5. Epub 2003 Nov 20. Link to article on publisher's siteDOI
10.1074/jbc.M312043200Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33793PubMed ID
14630919Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1074/jbc.M312043200