Apoptosis-linked in vivo regulation of the tissue transglutaminase gene promoter

Tissue transglutaminase (tTG) is upregulated in various cells undergoing ap optosis. To investigate the transcriptional regulation of tTG a mouse strai n carrying a beta -galactosidase reporter gene under the control of a 3.8 k ilobase fragment of the tTG promoter was characterised. The transgene const ruct was shown to be expressed in the apoptotic regions of the mouse embryo . Here we report that the regulation of the transgene is also apoptosis-lin ked in adult animals. The transgene is induced in endocrine apoptosis invol ving mammary gland involution and corpus luteum regression. Induction of th e reporter gene is detectable during in vivo but not in vitro apoptosis of thymocytes induced by the glucocorticoid receptor, the nur77, p53 and the r etinoid receptor gamma mediated pathways. Additionally, the lacZ expression mimics the activation of the endogenous promoter in tissues characterised by high apoptotic turnover. These results suggest that the apoptosis-specif ic transcriptional regulation of tTG is mediated through elements of a 3.8 kb promoter and may require cosignals available only in tissue environment.