Loss of the INI1 tumor suppressor does not impair the expression of multiple BRG1-dependent genes or the assembly of SWI/SNF enzymes.
The INI1/hSNF5 tumor suppressor is an integral component of mammalian SWI/SNF chromatin remodeling enzymes that contain SNF2 family ATPases BRM (Brahma) or BRG1 (Brahma Related Gene 1) and that contribute to the regulation of many genes. Genetic studies of yeast SWI/SNF enzyme revealed similar phenotypes when single or multiple components of the enzyme were deleted, indicating a requirement for each subunit. To address the contribution of INI1 in the regulation of SWI/SNF-dependent genes in mammalian cells, we examined the expression of multiple BRG1-dependent, constitutively expressed genes in INI1-deficient cancer cell lines. At least one INI1-deficient line expressed each gene, and reintroduction of INI1 had negligible effects on expression levels. Lack of INI1 also did not prevent interferon gamma (IFNgamma)-mediated induction of CIITA, which is BRG1 dependent, and GBP-1, which is BRG1 enhanced, and reintroduction of INI1 had minimal effects. Chromatin immunoprecipitation experiments revealed that BRG1 inducibly binds to the CIITA promoter despite the absence of INI1. Unlike yeast deleted for the INI1 homologue, SWI/SNF enzymes in INI1-deficient cells were largely intact. Thus in human cells, SWI/SNF enzyme complex formation and the expression of many BRG1-dependent genes are independent of INI1.
Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Diem N
DN
Doan
Timothy M
TM
Veal
Zhijiang
Z
Yan
Weidong
W
Wang
Stephen N
SN
Jones
Anthony N
AN
Imbalzano
D000818:Animals; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000502:physiology*; D019204:GTP-Binding Proteins; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D009687:Nuclear Proteins / Q000502:physiology*; D011506:Proteins / Q000502:physiology; D011817:Rabbits; D000071796:SMARCB1 Protein; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology*
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C490287:GBP1 protein, human; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D011506:Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; C445179:SWI-SNF-B chromatin-remodeling complex; D015534:Trans-Activators; D014157:Transcription Factors; D007371:Interferon-gamma; D019204:GTP-Binding Proteins; C084108:SMARCA4 protein, human; D004265:DNA Helicases