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

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.

journal_name

Biol Chem

journal_title

Biological chemistry

authors

Wolf SS,Roder K,Sickinger S,Schweizer M

doi

10.1515/BC.2001.136

keywords:

subject

Has Abstract

pub_date

2001-07-01 00:00:00

pages

1083-8

issue

7

eissn

1431-6730

issn

1437-4315

journal_volume

382

pub_type

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