Selective coactivator interactions in gene activation by SREBP-1a and -1c

Julia I. Toth, Shrimati Datta, Jyoti N. Athanikar, Leonard P. Freedman, Timothy Osborne

Research output: Contribution to journalArticle

Abstract

Requisite levels of intracellular cholesterol and fatty acids are maintained in part by the sterol regulatory element binding proteins (SREBPs). Three major SREBP isoforms exist; SREBP-1a and SREBP-1c are expressed from overlapping mRNAs, whereas SREBP-2 is encoded by a separate gene. The active forms of SREBP-1a and SREBP-1c differ only at their extreme N termini; SREBP-1c lacks 28 aa present in SREBP-1a and instead contains 4 unique aa of its own. While the SREBP-1a and -1c isoforms differentially activate transcription, the molecular basis of this difference is unknown. Here we define the differences between these proteins that confer the enhanced activity of SREBP-1a and demonstrate that this enhancement is a direct result of its avid binding to the coactivator CREB binding protein (CBP) and the mammalian mediator complex. While previous work determined that the C/H1 zinc finger and KIX domains of CBP bind to SREBP-1a, we provide evidence that the interaction with C/H1 is important for gene activation. We further show that the association between the activation domain of SREBP-1 and mediator is through aa 500 to 824 of DRIP150. Finally, we demonstrate the recruitment of mediator to an SREBP-responsive promoter in a sterol-dependent manner.

Original languageEnglish (US)
Pages (from-to)8288-8300
Number of pages13
JournalMolecular and Cellular Biology
Volume24
Issue number18
DOIs
StatePublished - Sep 1 2004
Externally publishedYes

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Sterol Regulatory Element Binding Protein 1
Transcriptional Activation
Sterol Regulatory Element Binding Proteins
CREB-Binding Protein
Protein Isoforms
Sterol Regulatory Element Binding Protein 2
Mediator Complex
Zinc Fingers
Sterols
Fatty Acids

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Selective coactivator interactions in gene activation by SREBP-1a and -1c. / Toth, Julia I.; Datta, Shrimati; Athanikar, Jyoti N.; Freedman, Leonard P.; Osborne, Timothy.

In: Molecular and Cellular Biology, Vol. 24, No. 18, 01.09.2004, p. 8288-8300.

Research output: Contribution to journalArticle

Toth, Julia I. ; Datta, Shrimati ; Athanikar, Jyoti N. ; Freedman, Leonard P. ; Osborne, Timothy. / Selective coactivator interactions in gene activation by SREBP-1a and -1c. In: Molecular and Cellular Biology. 2004 ; Vol. 24, No. 18. pp. 8288-8300.
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