Transcriptional regulation of the rat platelet factor 4 gene: interaction between an enhancer/silencer domain and the GATA site - PubMed (original) (raw)

Transcriptional regulation of the rat platelet factor 4 gene: interaction between an enhancer/silencer domain and the GATA site

K Ravid et al. Mol Cell Biol. 1991 Dec.

Abstract

We used various segments of the 5' upstream region of the rat platelet factor 4 (PF4) gene coupled to the human growth hormone gene and heterologous promoters to identify domains which are critical for tissue-specific expression. Transient expression experiments with rat bone marrow cells and other cell lines revealed a complex interplay between a core promoter domain from -97 to the transcriptional start site and an enhancer/silencer domain from -448 to -112. The core promoter contains a GATA site at -31 to -28 whose mutation to TATA or AATA decreases tissue specificity and moderately affects expression in megakaryocytes as well as a positively acting subdomain from -97 to -83 whose removal decreases overall transcription without affecting tissue specificity. The enhancer/silencer domain possesses three positively acting subdomains from -380 to -362, -270 to -257, and -137 to -120 as well as a negatively acting subdomain at -184 to -151 which is able to reduce overall transcription but has no effect on tissue specificity. The subdomain from -380 to -362 is most critical in restricting gene expression driven either by the PF4 promoter or by a heterologous promoter to the megakaryocytic lineage. The subdomains from -270 to -257 and -137 to -120 function together with the subdomain from -380 to -362 to somewhat increase tissue specificity. Simultaneous mutation of the GATA site and deletion of either the whole enhancer/silencer domain or the subdomain from -380 to -362 or -137 to -120 reduce transcription in megakaryocytes by 10- to 30-fold. On the basis of the above-described results, we propose that the megakaryocyte-specific enhancer/silencer domain and the GATA site are responsible for high-level expression of the PF4 gene in a lineage-specific manner.

PubMed Disclaimer

Cited by

Multiple ETS family proteins regulate PF4 gene expression by binding to the same ETS binding site.
Okada Y, Nobori H, Shimizu M, Watanabe M, Yonekura M, Nakai T, Kamikawa Y, Wakimura A, Funahashi N, Naruse H, Watanabe A, Yamasaki D, Fukada S, Yasui K, Matsumoto K, Sato T, Kitajima K, Nakano T, Aird WC, Doi T. Okada Y, et al. PLoS One. 2011;6(9):e24837. doi: 10.1371/journal.pone.0024837. Epub 2011 Sep 12. PLoS One. 2011. PMID: 21931859 Free PMC article.
The A2b adenosine receptor protects against vascular injury.
Yang D, Koupenova M, McCrann DJ, Kopeikina KJ, Kagan HM, Schreiber BM, Ravid K. Yang D, et al. Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):792-6. doi: 10.1073/pnas.0705563105. Epub 2008 Jan 9. Proc Natl Acad Sci U S A. 2008. PMID: 18184815 Free PMC article.
B-Myb regulates the A(2B) adenosine receptor in vascular smooth muscle cells.
St Hilaire C, Yang D, Schreiber BM, Ravid K. St Hilaire C, et al. J Cell Biochem. 2008 Apr 15;103(6):1962-74. doi: 10.1002/jcb.21586. J Cell Biochem. 2008. PMID: 17979185 Free PMC article.
The A2B adenosine receptor protects against inflammation and excessive vascular adhesion.
Yang D, Zhang Y, Nguyen HG, Koupenova M, Chauhan AK, Makitalo M, Jones MR, St Hilaire C, Seldin DC, Toselli P, Lamperti E, Schreiber BM, Gavras H, Wagner DD, Ravid K. Yang D, et al. J Clin Invest. 2006 Jul;116(7):1913-23. doi: 10.1172/JCI27933. J Clin Invest. 2006. PMID: 16823489 Free PMC article.
Maturation stage-specific regulation of megakaryopoiesis by pointed-domain Ets proteins.
Pang L, Xue HH, Szalai G, Wang X, Wang Y, Watson DK, Leonard WJ, Blobel GA, Poncz M. Pang L, et al. Blood. 2006 Oct 1;108(7):2198-206. doi: 10.1182/blood-2006-04-019760. Epub 2006 Jun 6. Blood. 2006. PMID: 16757682 Free PMC article.

References

1. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4584-7 - PubMed
1. J Exp Med. 1981 Jul 1;154(1):88-100 - PubMed
1. J Cell Biol. 1983 Feb;96(2):515-20 - PubMed
1. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 - PubMed
1. Blood. 1984 Apr;63(4):768-78 - PubMed

Transcriptional regulation of the rat platelet factor 4 gene: interaction between an enhancer/silencer domain and the GATA site - PubMed (original) (raw)