Peter Weil
Faculty Member
Last active: 11/4/2015

Suppression of intragenic transcription requires the MOT1 and NC2 regulators of TATA-binding protein.

Koster MJ, Yildirim AD, Weil PA, Holstege FC, Timmers HT
Nucleic Acids Res. 2014 42 (7): 4220-9

PMID: 24459134 · PMCID: PMC3985625 · DOI:10.1093/nar/gkt1398

Chromatin structure in transcribed regions poses a barrier for intragenic transcription. In a comprehensive study of the yeast chromatin remodelers and the Mot1p-NC2 regulators of TATA-binding protein (TBP), we detected synthetic genetic interactions indicative of suppression of intragenic transcription. Conditional depletion of Mot1p or NC2 in absence of the ISW1 remodeler, but not in the absence of other chromatin remodelers, activated the cryptic FLO8 promoter. Likewise, conditional depletion of Mot1p or NC2 in deletion backgrounds of the H3K36 methyltransferase Set2p or the Asf1p-Rtt106p histone H3-H4 chaperones, important factors involved in maintaining a repressive chromatin environment, resulted in increased intragenic FLO8 transcripts. Activity of the cryptic FLO8 promoter is associated with reduced H3 levels, increased TBP binding and tri-methylation of H3K4 and is independent of Spt-Ada-Gcn5-acetyltransferase function. These data reveal cooperation of negative regulation of TBP with specific chromatin regulators to inhibit intragenic transcription.

MeSH Terms (16)

Adenosine Triphosphatases Alleles Chromatin DNA-Binding Proteins Gene Expression Regulation, Fungal Nuclear Proteins Phosphoproteins Promoter Regions, Genetic Repressor Proteins Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins TATA-Binding Protein Associated Factors TATA-Box Binding Protein Trans-Activators Transcription, Genetic Transcription Factors

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