The promoter of the mouse tissue transglutaminase gene directs tissue-specific, retinoid-regulated and apoptosis-linked expression

L. Nagy, Vilmos A. Thomázy, Margaret M. Saydak, Joseph P. Stein, Peter J A Davies

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Tissue transglutaminase is a multifunctional enzyme that accumulates to high levels in cells undergoing apoptosis. Retinoids act as an acute and direct regulator of tissue transglutaminase gene transcription. The studies reported here were carried out to elucidate the molecular mechanisms involved in the regulation of tissue transglutaminase expression. We have isolated and characterized the mouse tissue transglutaminase gene promoter and 3.8 kb of 5′-flanking DNA. A large fragment of the promoter that includes both the core promoter and 3.8 kb of 5′-flanking DNA shows retinoid-dependent transcriptional activity when stably transfected into HeLa cells. In these stably transfected HeLa cells both the endogenous tissue transglutaminase gene and transfected mouse tissue transglutaminase promoter are activated by all-trans retinoic acid and by retinoic acid receptor (RAR)-specific and retinoid X receptor (RXR)-specific retinoids. In embryos made transgenic with a transglutaminase promoter-β-galactosidase reporter gene, the transgene shows specific patterns of expression during limb development. The transglutaminase transgene is expressed in cartilage, the cells of the apical ectodermal ridge, and in regions of apoptotic cell death of the interdigital mesenchyme. It appears that cis-acting elements responsible for the complex retinoid regulation, tissue- and apoptosis-specific expression are embedded within the proximal 3.8 kb of DNA flanking the 5′-end of the mouse tissue transglutaminase gene.

Original languageEnglish
Pages (from-to)534-547
Number of pages14
JournalCell Death and Differentiation
Volume4
Issue number7
Publication statusPublished - 1997

Fingerprint

Retinoids
Apoptosis
Genes
Transglutaminases
Transgenes
HeLa Cells
DNA
Multifunctional Enzymes
Galactosidases
Retinoid X Receptors
Retinoic Acid Receptors
Mesoderm
Tretinoin
transglutaminase 2
Reporter Genes
Cartilage
Cell Death
Embryonic Structures
Extremities

Keywords

  • Apoptosis
  • Gene
  • Promoter
  • Retinoids
  • Tissue transglutaminase
  • Transgene

ASJC Scopus subject areas

  • Cell Biology

Cite this

The promoter of the mouse tissue transglutaminase gene directs tissue-specific, retinoid-regulated and apoptosis-linked expression. / Nagy, L.; Thomázy, Vilmos A.; Saydak, Margaret M.; Stein, Joseph P.; Davies, Peter J A.

In: Cell Death and Differentiation, Vol. 4, No. 7, 1997, p. 534-547.

Research output: Contribution to journalArticle

Nagy, L. ; Thomázy, Vilmos A. ; Saydak, Margaret M. ; Stein, Joseph P. ; Davies, Peter J A. / The promoter of the mouse tissue transglutaminase gene directs tissue-specific, retinoid-regulated and apoptosis-linked expression. In: Cell Death and Differentiation. 1997 ; Vol. 4, No. 7. pp. 534-547.
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