Characterization of the structure and function of the gene for transcription factor BF-1, an essential regulator of forebrain development.
Brain factor-1 (BF-1) is a winged-helix transcription factor which has been shown to be essential for the development of the cerebral hemispheres. We report here the cloning and characterization of the mouse BF-1 gene. We have identified two classes of alternatively spliced mouse BF-1 cDNA which are transcribed from distinct promoters. Both classes of cDNA encode identical BF-1 proteins. The class 1 mouse cDNA is the homolog of the previously reported rat and human BF-1 cDNAs, and accounts for about 90-95% of BF-1 expression in brain. Primer extension analyses show that the major promoter, P1, is TATA-less and has multiple transcription start sites. We identified neural cell lines which express BF-1 primarily from the P1 promoter, including the OBL21a and OBL21 cell lines derived from the olfactory bulb. Expression of BF-1 is highest in proliferating OBL21 cells, declining as the cells differentiate in vitro. This correlates well with the reduction of BF-1 expression as the cells of the telencephalic neuroepithelium differentiate. Using these cells, we demonstrate that the genomic region between -3.7kb and -79 bp upstream of the P1 promoter contains cell-specific enhancer activity in transient transfection assays.
Li
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H
Molecular Biology Program, Sloan-Kettering Division, Cornell University Graduate School of Medical Sciences, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Tao
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W
Lai
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D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D051858:Forkhead Transcription Factors; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000502:physiology*; D016548:Prosencephalon / Q000254:growth & development*; D051381:Rats; D014157:Transcription Factors / Q000502:physiology*; D000071161:Forkhead Box Protein O1
D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C489562:Foxd1 protein, mouse; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1