The Set2/Rpd3S pathway suppresses cryptic transcription without regard to gene length or transcription frequency.
In cells lacking the histone methyltransferase Set2, initiation of RNA polymerase II transcription occurs inappropriately within the protein-coding regions of genes, rather than being restricted to the proximal promoter. It was previously reported that this "cryptic" transcription occurs preferentially in long genes, and in genes that are infrequently transcribed. Here, we mapped the transcripts produced in an S. cerevisiae strain lacking Set2, and applied rigorous statistical methods to identify sites of cryptic transcription at high resolution. We find that suppression of cryptic transcription occurs independent of gene length or transcriptional frequency. Our conclusions differ with those reported previously because we obtained a higher-resolution dataset, we accounted for the fact that gene length and transcriptional frequency are not independent variables, and we accounted for several ascertainment biases that make cryptic transcription easier to detect in long, infrequently transcribed genes. These new results and conclusions have implications for many commonly used genomic analysis approaches, and for the evolution of high-fidelity RNA polymerase II transcriptional initiation in eukaryotes.
Lickwar
Colin R
CR
Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Rao
Bhargavi
B
Shabalin
Andrey A
AA
Nobel
Andrew B
AB
Strahl
Brian D
BD
Lieb
Jason D
JD
D000465:Algorithms; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D011401:Promoter Regions, Genetic; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D029701:Saccharomyces cerevisiae Proteins; D012313:RNA; D008780:Methyltransferases; C448996:Set2 protein, S cerevisiae; D012319:RNA Polymerase II; C071665:RPD3 protein, S cerevisiae; D006655:Histone Deacetylases