Exp Mol Med.  2004 Aug;36(4):300-310.

Weakening of the repressive YY-1 site on the thrombospondin-1 promoter via c-Jun/YY-1 interaction

Affiliations
  • 1Department of Biochemistry College of Medicine, The Catholic University of Korea 505 Banpo-dong, Socho-gu Seoul 137-701, Korea. kjhong@catholic.ac.kr
  • 2Department of Pathology College of Medicine The Chosun University of Korea Seoseok-dong, Dong-gu Gwangju 501-759, Korea.
  • 3Department of Bioscience and Biotechnology Sejong University, 98 Gunja-dong Gwangjin-gu, Seoul 143-747, Korea.

Abstract

Thrombospondin-1 (TSP-1) level is tightly regulated at the transcriptional level. To determine the detailed molecular mechanisms of TSP-1 expression, nine serial 5'-deletion constructs of the human genomic tsp-1 promoter (nucleotides -2,220 to +756) were prepared, inserted into luciferase reporter plasmids, and transiently transfected into the Hep3B human hepatocarcinoma cell. Among the nine 5'-deletion constructs, pTSP-Luc-4 (-767~+756) had consistently decreased luciferase activity with or without PMA stimulation, whereas a further truncated construct [pTSP-Luc-4' (-407~+756)] had increased levels of expression. By searching the nucleotides from -767 to -407, a consensus binding sequence (5'-CCATTTT-3') for the repressor Yin Yang-1 (YY-1) at nucleotide -440 was identified. The suppression induced by this site was weakened in the presence of the region upstream of nucleotide -767 (pTSP-Luc-1 and -2). Nuclear protein directly bound to an oligonucleotide containing the repressive YY-1 sequence but the binding capacity of the sequence was decreased by the increased c-Jun levels. Moreover, proteins immunoprecipitated with anti-YY-1 revealed an interaction between c-Jun and YY-1 factor. These data suggest that the repressive YY-1 site of the tsp-1 promoter could not be functional via activating positive cis-elements on the upstream from this site and weakened via c-Jun/YY-1 interactions.

Keyword

c-Jun; gene expression; promoter; TSP-1; YY-1
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