Title

Transcriptional compensation for loss of an allele of the Ini1 tumor suppressor

Student Author(s)

Cynthia J. Guidi

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

Link to article in PubMed

PubMed ID

14630919

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