Apoptosis-linked in vivo regulation of the tissue transglutaminase gene promoter.
Tissue transglutaminase (tTG) is upregulated in various cells undergoing apoptosis. To investigate the transcriptional regulation of tTG a mouse strain carrying a beta-galactosidase reporter gene under the control of a 3.8 kilobase fragment of the tTG promoter was characterised. The transgene construct 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-linked in adult animals. The transgene is induced in endocrine apoptosis involving mammary gland involution and corpus luteum regression. Induction of the reporter gene is detectable during in vivo but not in vitro apoptosis of thymocytes induced by the glucocorticoid receptor, the nur77, p53 and the retinoid 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-specific transcriptional regulation of tTG is mediated through elements of a 3.8 kb promoter and may require cosignals available only in tissue environment. Cell Death and Differentiation (2000) 7, 1225 - 1233.
Szegezdi
E
E
Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary.
Szondy
Z
Z
Nagy
L
L
Nemes
Z
Z
Friis
R R
RR
Davies
P J
PJ
Fésüs
L
L
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001940:Breast / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D005809:Genes, Regulator / Q000502:physiology; D017930:Genes, Reporter / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic / Q000378:metabolism; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism; D019076:Transgenes / Q000502:physiology; D011503:Transglutaminases / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics*; D001616:beta-Galactosidase / Q000235:genetics
D012333:RNA, Messenger; D011503:Transglutaminases; D001616:beta-Galactosidase