Journal article
Characterisation of PAUSE-1, a powerful silencer in the human plasminogen activator inhibitor type 2 gene promoter
Nucleic Acids Research, Vol.29(19), pp.3919-3927
2001
Abstract
Plasminogen activator inhibitor type 2 (PAI-2) is a serine protease inhibitor traditionally regarded as a regulator of fibrinolysis and extracellular matrix degradation. More recently, PAI-2 has been implicated in diverse processes such as keratinocyte differentiation, cell death and viral pathogenesis. The PAI-2 promoter tightly regulates PAI-2 gene expression in a cell-specific manner and this control is mediated, in part, by the upstream silencer element, PAUSE-1. Here we have defined PAUSE-1 and investigated its activity as a silencer. A series of mutations were generated within the PAUSE-1 element and analysed for transcription factor binding and transcriptional silencing activity. These studies have defined the minimal functional PAUSE-1 element as TCTNxAGAN3T4, where x = 0, 2 or 4. Examination of related elements present in other promoters, such as the human IFNβ promoter, suggests that PAUSE-1 is a member of a family of universal silencers with the consensus sequence TCTNxAGA. UV crosslinking analyses determined that the PAUSE-1 binding protein was ∼67 kDa. Insertion of PAUSE-1 into the heterologous (SV40) or the minimal PAI-2 promoters silenced transcription by 2.5-fold. These data show that PAUSE-1 acts as a powerful silencer of PAI-2 gene transcription and is likely to be important in the silencing of other genes as well.
Details
- Title
- Characterisation of PAUSE-1, a powerful silencer in the human plasminogen activator inhibitor type 2 gene promoter
- Authors
- Steven Ogbourne (Author) - Queensland Institute of Medical ResearchT M Antalis (Author) - Queensland Institute of Medical Research
- Publication details
- Nucleic Acids Research, Vol.29(19), pp.3919-3927
- Publisher
- Oxford University Press
- Date published
- 2001
- DOI
- 10.1093/nar/29.19.3919
- ISSN
- 0305-1048
- Organisation Unit
- School of Science and Engineering - Legacy; University of the Sunshine Coast, Queensland; School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 99450113602621
- Output Type
- Journal article
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