Title
Transcriptional compensation for loss of an allele of the Ini1 tumor suppressor
Academic Program
Cell Biology
UMMS Affiliation
Department of Cell Biology
Publication Date
2004-02-06
Document Type
Article
Disciplines
Cell Biology | Life Sciences | Medicine and Health Sciences
Abstract
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.
DOI of Published Version
10.1074/jbc.M312043200
Source
J Biol Chem. 2004 Feb 6;279(6):4180-5. Epub 2003 Nov 20. Link to article on publisher's site
Journal/Book/Conference Title
The Journal of biological chemistry
Related Resources
PubMed ID
14630919
Repository Citation
Guidi CJ, Veal TM, Jones SN, Imbalzano AN. (2004). Transcriptional compensation for loss of an allele of the Ini1 tumor suppressor. GSBS Student Publications. https://doi.org/10.1074/jbc.M312043200. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/455