Genomic association of the proteasome demonstrates overlapping gene regulatory activity with transcription factor substrates.
The proteasome can regulate transcription through proteolytic processing of transcription factors and via gene locus binding, but few targets of proteasomal regulation have been identified. Using genome-wide location analysis and transcriptional profiling in Saccharomyces cerevisiae, we have established which genes are bound and regulated by the proteasome and by Spt23 and Mga2, transcription factors activated by the proteasome. We observed proteasome association with gene sets that are highly transcribed, controlled by the mating type loci, and involved in lipid metabolism. At ribosomal protein (RP) genes, proteasome and RNA polymerase II (RNA Pol II) binding was enriched in a proteasome mutant, indicating a role for the proteasome in dissociating elongation complexes. The genomic occupancies of Spt23 and Mga2 overlapped significantly with the genes bound by the proteasome. Finally, the proteasome acts in two distinct ways, one dependent and one independent of Spt23/Mga2 cleavage, providing evidence for cooperative gene regulation by the proteasome and its substrates.
Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Kathryn L
KL
Auld
Christopher R
CR
Brown
Jason M
JM
Casolari
Suzanne
S
Komili
Pamela A
PA
Silver
D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D005807:Genes, Overlapping; D008565:Membrane Proteins; D046988:Proteasome Endopeptidase Complex / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D013489:Suppression, Genetic / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; C542266:MGA2 protein, S cerevisiae; D008565:Membrane Proteins; C087570:SPT23 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D046988:Proteasome Endopeptidase Complex