Transcription of the LAT gene is regulated by multiple binding sites for Sp1 and Sp3

The LAT gene encodes an adaptor molecule that links receptor engagement to critical downstream signaling events. Previously, we identified the proximal promoter for the human LAT gene and found that it contains binding sites for members of the Ets and Runx transcription factor families. In the present study, we show that the promoter also contains 5 GC-rich elements that contribute to promoter activity and that are capable of binding the transcription factors Sp1 and Sp3. Overexpression of either Sp1 or full-length Sp3 was shown to augment LAT promoter activity, while siRNA-mediated knockdown of each transcription factor was demonstrated to have an inhibitory effect. We also discovered a cell-type specific DNase hypersensitive site that maps to the Sp1/Sp3 and adjacent Ets and Runx binding sites. Collectively, these results provide compelling data that implicates Sp1 and Sp3 in the transcriptional regulation of the human LAT gene. (c) 2008 Elsevier B.V. All rights reserved.