Regulation of the plasminogen activator inhibitor type-2 gene in monocytes: localization of an upstream transcriptional silencer - PubMed (original) (raw)
. 1996 Nov 15;88(10):3686-97.
Affiliations
- PMID: 8916932
Free article
Regulation of the plasminogen activator inhibitor type-2 gene in monocytes: localization of an upstream transcriptional silencer
T M Antalis et al. Blood. 1996.
Free article
Abstract
Transcriptional regulation of the plasminogen activator inhibitor type-2 (PAI-2) gene appears to be an important factor in the response of mononuclear phagocytes to inflammation. We have investigated here the molecular basis for PAI-2 synthesis in monocytic cells by reporter gene deletion analysis. A DNA fragment containing 5.1 kb of 5' flanking region through to the start of the second exon was fused to a chloramphenicol acetyl transferase (CAT) reporter gene, transfected into macrophage and nonmacrophage cells and tested for PAI-2 promoter-directed CAT activity in the presence and absence of phorbol ester. Deletion analysis showed the existence of three major transcription regulatory regions. (1) A positive regulatory region contained in the proximal promoter mediates basal transcription and 12-phorbol 13-myristate acetate inducibility. (2) A negative regulatory region, or silencer, present between -1977 and -1675, was found to repress PAI-2 promoter activity in an orientation- and position-independent manner, but not in a cell-specific manner. (3) A second positive regulatory element, located upstream between approximately -5100 and -3300, appears to overcome inhibition mediated by the silencer in a cell-specific manner, suggesting a mechanism for the regulation of this gene. We have localized the motif responsible for silencer activity to a 28-bp DNA sequence containing a unique 12-bp palindrome centered at an Xba I restriction enzyme site, CTCTCTAGAGAG, which is designated the PAI-2-upstream silencer element-1 (PAUSE-1). This element binds a specific PAUSE-1 binding factor as determined by mobility shift analysis. We conclude that PAI-2 gene transcription is regulated by both positive and negative control mechanisms that may be important for the regulation of other genes as well.
Similar articles
- Plasminogen activator inhibitor type-2 (PAI-2) gene transcription requires a novel NF-kappaB-like transcriptional regulatory motif.
Mahony D, Kalionis B, Antalis TM. Mahony D, et al. Eur J Biochem. 1999 Aug;263(3):765-72. doi: 10.1046/j.1432-1327.1999.00552.x. Eur J Biochem. 1999. PMID: 10469140 - Regulation of the human plasminogen activator inhibitor type 2 gene: cooperation of an upstream silencer and transactivator.
Stringer B, Udofa EA, Antalis TM. Stringer B, et al. J Biol Chem. 2012 Mar 23;287(13):10579-10589. doi: 10.1074/jbc.M111.318758. Epub 2012 Feb 9. J Biol Chem. 2012. PMID: 22334683 Free PMC article. - [Regulation mechanism of specific expression of tumor marker gene during carcinogenesis].
Imagawa M. Imagawa M. Yakugaku Zasshi. 1996 Jul;116(7):505-18. doi: 10.1248/yakushi1947.116.7_505. Yakugaku Zasshi. 1996. PMID: 8831256 Review. Japanese. - Identification and characterization of transcriptional regulatory elements of the human aromatase cytochrome P450 gene (CYP19).
Toda K, Nomoto S, Shizuta Y. Toda K, et al. J Steroid Biochem Mol Biol. 1996 Jan;56(1-6 Spec No):151-9. doi: 10.1016/0960-0760(95)00232-4. J Steroid Biochem Mol Biol. 1996. PMID: 8603036 Review.
Cited by
- Long-Distance Repression by Human Silencers: Chromatin Interactions and Phase Separation in Silencers.
Zhang Y, See YX, Tergaonkar V, Fullwood MJ. Zhang Y, et al. Cells. 2022 May 5;11(9):1560. doi: 10.3390/cells11091560. Cells. 2022. PMID: 35563864 Free PMC article. Review. - Gastrin activates paracrine networks leading to induction of PAI-2 via MAZ and ASC-1.
Almeida-Vega S, Catlow K, Kenny S, Dimaline R, Varro A. Almeida-Vega S, et al. Am J Physiol Gastrointest Liver Physiol. 2009 Feb;296(2):G414-23. doi: 10.1152/ajpgi.90340.2008. Epub 2008 Dec 12. Am J Physiol Gastrointest Liver Physiol. 2009. PMID: 19074642 Free PMC article. - Transcriptional control and the role of silencers in transcriptional regulation in eukaryotes.
Ogbourne S, Antalis TM. Ogbourne S, et al. Biochem J. 1998 Apr 1;331 ( Pt 1)(Pt 1):1-14. doi: 10.1042/bj3310001. Biochem J. 1998. PMID: 9512455 Free PMC article. Review. - SilenceREIN: seeking silencers on anchors of chromatin loops by deep graph neural networks.
Pan JH, Du PF. Pan JH, et al. Brief Bioinform. 2023 Nov 22;25(1):bbad494. doi: 10.1093/bib/bbad494. Brief Bioinform. 2023. PMID: 38168841 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous