A novel lineage-specific hypersensitive site is essential for position independent granzyme B expression in transgenic mice
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- 作者：Brenda L. Duggan ; Nora R. Cabilio ; Peter Dickie ; Jennifer Witmer ; Ing Swie Goping ; D. Alan Underhill ; R. Chris Bleackley
- 关键词：Granzyme B ; Gene regulation ; DNase hypersensitivity ; Transgenic ; Cytotoxic T cell
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2008
- 出版时间：4 April 2008
- 年：2008
- 卷：368
- 期：2
- 页码：357-363
- 全文大小：291 K
文摘
The granzyme B gene is activated upon cytotoxic T cell stimulation and the protein is a key inducer of apoptosis in target cells. Previous studies have identified important proximal regulatory regions but these proved insufficient to drive expression in vivo. We identified a DNase1 hypersensitive site (HS2) 3.9 kb upstream of the transcription start site that was present in stimulated but not resting CD8+ cells. The CTL line CTLL R8 was stably transfected with GFP reporter constructs and showed consistently higher fluorescence values when HS2 was included. In transgenic mice the presence of the relevant region of DNA resulted in inducible, CTL-specific transcription of the transgene in all transgenic founder lines analyzed. Deletion of HS2 resulted in a 10-fold reduction in expression. This is the first report of a major distal regulatory element in the control of granzyme B transcription.