The FIRE3-mediated sterol response of the FAS promoter requires NF-Y/CBF as coactivator

S. S. Wolf, K. Roder, S. Sickinger, M. Schweizer

    Research output: Contribution to journalArticle

    5 Citations (Scopus)

    Abstract

    The transcription of the fatty acid synthase (FAS) gene is regulated by the sterol status of the cell via cleavage of the sterol regulatory element-binding protein (SREBP). When human HepG2 hepatoma cells were cotransfected with an expression plasmid for mature SREBP-1a together with FAS promoter/reporter constructs significant increases in reporter activity were observed. Deletion analysis of the FAS promoter between -151 and -52 relative to the transcription start site pinpoint two cis-elements important in sterol regulation of the FAS gene. One element, FIRE3, between -71 and -52 can bind in vitro translated and transcribed SREBP-1a whereas the other element, the inverted CCAAT element ICE(-97/-92), binds the trimeric transcription factor NF-Y/CBF as shown with rat liver extract and reconstituted, recombinant NF-Y. The results clearly show that the coactivator for SREBP-1a in this cell line is NF-Y. This finding was confirmed by using a dominant negative form of NF-YA, NF-YAm29, which interferes with the effect of ectopically expressed SREBP-1a on FAS reporter activity.

    Original languageEnglish
    Pages (from-to)1083-1088
    Number of pages6
    JournalBiological Chemistry
    Volume382
    Issue number7
    DOIs
    Publication statusPublished - 2001

    Keywords

    • Fatty acid synthase gene
    • HepG2
    • NF-Y
    • Sp1
    • SREBP

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