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Regulation of the human LAT gene by Ets and Sp/KLF transcription factors
Author(s) -
Finco Timothy Scott,
Hamilton Victoria E,
Patel Shivani J,
Zheng Cindy,
Justice Geri E
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a82-a
Subject(s) - ets transcription factor family , promoter , transcription factor , gene , biology , transcription (linguistics) , response element , microbiology and biotechnology , regulation of gene expression , gene expression , transcriptional regulation , genetics , linguistics , philosophy
The mammalian LAT gene encodes an adaptor protein critical for various signal transduction processes, including those initiated by the T cell receptor on T cells and the FcεRI receptor on mast cells. As a first step toward understanding the mechanisms responsible for the cell‐type restricted expression of the LAT gene, we have cloned and characterized its 5′ proximal promoter. We find that the promoter spans approximately 800 bp and contains both positive and negative regulatory elements. Within the promoter are two binding sites for the Ets family of transcription factors, one of which is adjacent to a binding site for Runx transcription factors. Both Ets sites can bind Elf‐1 while the Ets/Runx site binds a complex containing Runx1 and Ets‐1. The promoter also contains a number of G/C‐rich sites that bind Sp1 and Sp3. Point mutations in either the Ets or G/C‐rich sites abrogate promoter activity and inhibit the ability of these transcription factors to activate LAT gene expression. Collectively, this initial study into the transcriptional regulation of the human LAT gene identifies a number of important transcription factors governing its expression. The research is supported by a grant (MCB 0234997) from the National Science Foundation.