Upstream elements bestow T-cell and haemopoietic progenitor-specific activity on the granzyme B promoter.
AuthorsJohnson, Barbra A
John, Victoria A
Hampson, Ian N
Heyworth, Clare M
Babichuk, Charolyn K
Bleackley, R Chris
Dexter, T Michael
Cross, Michael A
AffiliationSection of Haemopoietic Cell and Gene Therapeutics, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, UK.
MetadataShow full item record
AbstractCytotoxic T cells and early haemopoietic progenitors share the expression of a number of specific genes. Of these, granzyme B has attracted particular interest because of its role in inducing apoptosis during cytotoxic T cell-mediated target cell killing, and its potential role in the mobilisation and homeostasis of haemopoietic stem cells. Studies of granzyme B regulation should therefore yield valuable information concerning the molecular control of these processes, and also identify elements capable of directing gene expression to two cell types of relevance to gene therapy. Here we show that proximal regulatory elements already known to direct promoter activity in T cells are similarly active in haemopoietic progenitors. However, this activity is not strictly specific, since the promoter regions also direct low levels of reporter gene expression in fibroblasts. More importantly, we also report the presence of two previously unidentified clusters of DNaseI hypersensitive sites upstream from the murine granzyme B gene, and show that these regions impart both increased transcriptional activity and the appropriate cell type specificity on the granzyme B promoter. These upstream regulatory regions are therefore likely to play a key role in the coordination of granzyme B expression in vivo.
CitationUpstream elements bestow T-cell and haemopoietic progenitor-specific activity on the granzyme B promoter. 1999, 234 (1):101-7 Gene
- In vivo regulation of murine granzyme B gene transcription in activated primary T cells.
- Authors: Babichuk CK, Duggan BL, Bleackley RC
- Issue date: 1996 Jul 12
- Targeting gene expression to haemopoietic stem cells: a chromatin-dependent upstream element mediates cell type-specific expression of the stem cell antigen CD34.
- Authors: May G, Enver T
- Issue date: 1995 Feb 1
- Identification of human granzyme B promoter regulatory elements interacting with activated T-cell-specific proteins: implication of Ikaros and CBF binding sites in promoter activation.
- Authors: Wargnier A, Legros-Maida S, Bosselut R, Bourge JF, Lafaurie C, Ghysdael CJ, Sasportes M, Paul P
- Issue date: 1995 Jul 18
- Mutational analysis of the murine granzyme B gene promoter in primary T cells and a T cell clone.
- Authors: Babichuk CK, Bleackley RC
- Issue date: 1997 Jul 25
- Organization of the gene encoding the mouse T-cell-specific serine proteinase "granzyme A".
- Authors: Ebnet K, Kramer MD, Simon MM
- Issue date: 1992 Jul