PMID- 10400691
OWN - NLM
STAT- MEDLINE
DCOM- 19990819
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 29
DP  - 1999 Jul 16
TI  - Identification of conserved cis-elements and transcription factors required for
      sterol-regulated transcription of stearoyl-CoA desaturase 1 and 2.
PG  - 20603-10
AB  - We previously identified stearoyl-CoA desaturase 2 (SCD2) as a new member of the 
      family of genes that are transcriptionally regulated in response to changing
      levels of nuclear sterol regulatory element binding proteins (SREBPs) or
      adipocyte determination and differentiation factor 1 (ADD1). A novel sterol
      regulatory element (SRE) (5'-AGCAGATTGTG-3') identified in the proximal promoter 
      of the mouse SCD2 gene is required for induction of SCD2 promoter-reporter genes 
      in response to cellular sterol depletion (Tabor, D. E., Kim, J. B., Spiegelman,
      B. M., and Edwards, P. A. (1998) J. Biol. Chem. 273, 22052-22058). In this
      report, we demonstrate that this novel SRE is both present in the promoter of the
      SCD1 gene and is critical for the sterol-dependent transcription of SCD1
      promoter-reporter genes. Two conserved cis elements (5'-CCAAT-3') lie 5 and 48
      base pairs 3' of the novel SREs in the promoters of both the SCD1 and SCD2 murine
      genes. Mutation of either of these putative NF-Y binding sites attenuates the
      transcriptional activation of SCD1 or SCD2 promoter-reporter genes in response to
      cellular sterol deprivation. Induction of both reporter genes is also attenuated 
      when cells are cotransfected with dominant-negative forms of either NF-Y or
      SREBP. In addition, we demonstrate that the induction of SCD1 and SCD2 mRNAs that
      occurs during the differentiation of 3T3-L1 preadipocytes to adipocytes is
      paralleled by an increase in the levels of ADD1/SREBP-1c and that the SCD1 and
      SCD2 mRNAs are induced to even higher levels in response to ectopic expression of
      ADD1/SREBP-1c. We conclude that transcription of both SCD1 and SCD2 genes is
      responsive to cellular sterol levels and to the levels of nuclear SREBP/ADD1 and 
      that transcriptional induction requires three spatially conserved cis elements,
      that bind SREBP and NF-Y. Additional studies demonstrate that maximal
      transcriptional repression of SCD2 reporter genes in response to an exogenous
      polyunsaturated fatty acid is dependent upon the SRE and the adjacent CCAAT
      motif.
FAU - Tabor, D E
AU  - Tabor DE
AD  - Departments of Biological Chemistry, University of California, Los Angeles,
      California 90095, USA.
FAU - Kim, J B
AU  - Kim JB
FAU - Spiegelman, B M
AU  - Spiegelman BM
FAU - Edwards, P A
AU  - Edwards PA
LA  - eng
GR  - HL 30568/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Isoenzymes)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (SREBF1 protein, human)
RN  - 0 (Srebf1 protein, mouse)
RN  - 0 (Sterol Regulatory Element Binding Protein 1)
RN  - 0 (Transcription Factors)
RN  - EC 1.14.19.1 (Stearoyl-CoA Desaturase)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Base Sequence
MH  - CCAAT-Enhancer-Binding Proteins
MH  - Cell Line
MH  - DNA-Binding Proteins/genetics
MH  - Electrophoresis/methods
MH  - *Gene Expression Regulation, Enzymologic
MH  - Genes, Reporter
MH  - Humans
MH  - Isoenzymes/chemistry/*metabolism
MH  - Mice
MH  - Nuclear Proteins/genetics
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/genetics
MH  - Stearoyl-CoA Desaturase/chemistry/genetics/*metabolism
MH  - Sterol Regulatory Element Binding Protein 1
MH  - Transcription Factors/*metabolism
EDAT- 1999/07/10 00:00
MHDA- 1999/07/10 00:01
CRDT- 1999/07/10 00:00
PHST- 1999/07/10 00:00 [pubmed]
PHST- 1999/07/10 00:01 [medline]
PHST- 1999/07/10 00:00 [entrez]
AID - 10.1074/jbc.274.29.20603 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jul 16;274(29):20603-10. doi: 10.1074/jbc.274.29.20603.