Mediator subunit Gal11p/MED15 is required for fatty acid-dependent gene activation by yeast transcription Factor Oaf1p

Jitendra K. Thakur, Haribabu Arthanari, Fajun Yang, Katherine H. Chau, Gerhard Wagner, Anders M. Näär

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

The yeast zinc cluster transcription factor Oaf1p activates transcription of target genes in response to direct binding of fatty acids in a manner analogous to the vertebrate nuclear receptor peroxisome proliferator-activated receptorα (PPARα).PPARsand other metazoan nuclear receptors productively engage several distinct LXXLL motif-containing co-activators, including p160 family members and the TRAP220/MED1 subunit of the Mediator coactivator, to promote ligand-dependent gene activation. Yeast, however, does not appear to harbor LXXLL motif co-activators, and the mechanism of fatty acid-dependent gene activation by the yeast PPARα analog Oaf1p is unknown. Here we show that the yeast Mediator subunit Gal11p/MED15 and its activatortargeted KIX domain plays a critical role in fatty acid-dependent transcriptional regulation of fatty acid β-oxidation and peroxisomal genes by Oaf1p and for the ability of yeast to utilize fatty acids as a sole carbon source. Moreover, structural studies by NMR spectroscopy reveal that the Oaf1p activation domain interacts with the Gal11p/MED15 KIX domain in a manner similar to the yeast zinc cluster family member and xenobiotic receptor Pdr1p, revealing that the Gal11p/ MED15 KIX domain is a key target of several ligand-dependent transcription factors in yeast. Together with previous work showing that the Caenorhabditis elegans Gal11p/MED15 homolog MDT-15 plays a critical role in regulation of fatty acid metabolism by the nematode PPAR-like nuclear receptor NHR-49, the findings presented here provide evidence for an ancient and essential role of a Mediator co-activator subunit in regulation of fatty acid metabolism by nuclear receptor-like transcription factors in eukaryotes.

Original languageEnglish (US)
Pages (from-to)4422-4428
Number of pages7
JournalJournal of Biological Chemistry
Volume284
Issue number7
DOIs
StatePublished - Feb 13 2009
Externally publishedYes

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Yeast
Transcriptional Activation
Transcription Factors
Fatty Acids
Genes
Yeasts
Chemical activation
Cytoplasmic and Nuclear Receptors
Peroxisome Proliferator-Activated Receptors
Metabolism
Zinc
Mediator Complex Subunit 1
Ligands
Aptitude
Caenorhabditis elegans
Xenobiotics
Transcription
Ports and harbors
ST 679
Eukaryota

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Mediator subunit Gal11p/MED15 is required for fatty acid-dependent gene activation by yeast transcription Factor Oaf1p. / Thakur, Jitendra K.; Arthanari, Haribabu; Yang, Fajun; Chau, Katherine H.; Wagner, Gerhard; Näär, Anders M.

In: Journal of Biological Chemistry, Vol. 284, No. 7, 13.02.2009, p. 4422-4428.

Research output: Contribution to journalArticle

Thakur, Jitendra K. ; Arthanari, Haribabu ; Yang, Fajun ; Chau, Katherine H. ; Wagner, Gerhard ; Näär, Anders M. / Mediator subunit Gal11p/MED15 is required for fatty acid-dependent gene activation by yeast transcription Factor Oaf1p. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 7. pp. 4422-4428.
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