Regulation of the human LAT gene by the Elf-1 transcription factor.
BACKGROUND
The LAT gene encodes an intracellular adaptor protein that links cell-surface receptor engagement to numerous downstream signalling events, and thereby plays an integral role in the function of cell types that express the gene, including T cells, mast cells, natural killer cells, and platelets. To date, the mechanisms responsible for the transcriptional regulation of this gene have not been investigated.


RESULTS
In this study we have mapped the transcriptional start sites for the human LAT gene and localized the 5' and 3' boundaries of the proximal promoter. We find that the promoter contains both positive and negative regulatory regions, and that two binding sites for the Ets family of transcription factors have a strong, positive effect on gene expression. Each site binds the Ets family member Elf-1, and overexpression of Elf-1 augments LAT promoter activity. The promoter also contains a Runx binding site adjacent to one of the Ets sites. This site, which is shown to bind Runx-1, has an inhibitory effect on gene expression. Finally, data is also presented indicating that the identified promoter may regulate cell-type specific expression.


CONCLUSIONS
Collectively, these results provide the first insights into the transcriptional regulation of the LAT gene, including the discovery that the Ets transcription factor Elf-1 may play a central role in its expression.
Finco
Timothy S
TS
Department of Biology, Agnes Scott College, Decatur, GA 30030, USA. tfinco@agnesscott.edu
Justice-Healy
Geri E
GE
Patel
Shivani J
SJ
Hamilton
Victoria E
VE
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D050783:Proto-Oncogene Proteins c-ets / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D024363:Transcription Initiation Site; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D050676:Core Binding Factor Alpha 2 Subunit; C512897:ELF1 protein, human; C110810:LAT protein, human; D008565:Membrane Proteins; D009687:Nuclear Proteins; D050783:Proto-Oncogene Proteins c-ets; C493728:RUNX1 protein, human; D011994:Recombinant Proteins; D014157:Transcription Factors; D004247:DNA