Nuclear factor I regulates brain fatty acid-binding protein and glial fibrillary acidic protein gene expression in malignant glioma cell lines.
Glial fibrillary acidic protein (GFAP), an intermediate filament protein normally found in astrocytes, and the radial glial marker brain fatty acid-binding protein (B-FABP; also known as FABP7) are co-expressed in malignant glioma cell lines and tumors. Nuclear factor I (NFI) recognition sites have been identified in the B-FABP and GFAP promoters, and transcription of both genes is believed to be regulated by NFI. Here, we study the role of the different members of the NFI family in regulating endogenous and ectopic B-FABP and GFAP gene transcription in human malignant glioma cells. We show by gel shifts that all four members of the NFI family (NFIA, NFIB, NFIC, and NFIX) bind to B-FABP and GFAP NFI consensus sites. Over-expression of NFIs, in conjunction with mutation analysis of NFI consensus sites using a reporter gene assay, supports a role for all four NFIs in the regulation of the GFAP and B-FABP genes. Knock-down of single or combined NFIs reveals promoter-dependent and promoter-context-dependent interaction patterns and suggests cross talk between the different members of the NFI family. Our data indicate that the NFI family of transcription factors plays a key role in the regulation of both the B-FABP and GFAP genes in malignant glioma cells.
Brun
Miranda
M
Department of Oncology, Cross Cancer Institute, University of Alberta, Alberta, Canada.
Coles
Jeffrey E
JE
Monckton
Elizabeth A
EA
Glubrecht
Darryl D
DD
Bisgrove
Dwayne
D
Godbout
Roseline
R
D024509:3' Flanking Region / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D000071438:Fatty Acid-Binding Protein 7; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics*; D005910:Glioma / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D051839:NFI Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D002352:Carrier Proteins; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; D005904:Glial Fibrillary Acidic Protein; D051839:NFI Transcription Factors; D025521:Tumor Suppressor Proteins