Weakening of the repressive YY-1 site on the thrombospondin-1 promoter via c-Jun/YY-1 interaction
Experimental & Molecular Medicine
;
: 300-310, 2004.
Article
in English
| WPRIM
| ID: wpr-198864
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Repressor Proteins
/
Transcription Factors
/
Binding Sites
/
Down-Regulation
/
Promoter Regions, Genetic
/
Proto-Oncogene Proteins c-jun
/
Sequence Deletion
/
Genes, Reporter
/
Transcription Factor AP-1
/
Thrombospondin 1
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2004
Type:
Article
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