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{"title"=>"The set2/Rpd3S pathway suppresses cryptic transcription without regard to gene length or transcription frequency", "type"=>"journal", "authors"=>[{"first_name"=>"Colin R.", "last_name"=>"Lickwar", "scopus_author_id"=>"14630789900"}, {"first_name"=>"Bhargavi", "last_name"=>"Rao", "scopus_author_id"=>"8886942100"}, {"first_name"=>"Andrey A.", "last_name"=>"Shabalin", "scopus_author_id"=>"24167255500"}, {"first_name"=>"Andrew B.", "last_name"=>"Nobel", "scopus_author_id"=>"7003830644"}, {"first_name"=>"Brian D.", "last_name"=>"Strahl", "scopus_author_id"=>"6701692923"}, {"first_name"=>"Jason D.", "last_name"=>"Lieb", "scopus_author_id"=>"7005815585"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"354396108", "pmid"=>"19295910", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0004886", "sgr"=>"63349106578", "scopus"=>"2-s2.0-63349106578"}, "id"=>"d8a3fd07-0e8a-34bc-a48a-7f94bf76ff74", "abstract"=>"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.", "link"=>"http://www.mendeley.com/research/set2rpd3s-pathway-suppresses-cryptic-transcription-without-regard-gene-length-transcription-frequenc", "reader_count"=>51, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>6, "Researcher"=>11, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>20, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>4, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>6, "Researcher"=>11, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>20, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>4, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>14, "Agricultural and Biological Sciences"=>33, "Medicine and Dentistry"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>33}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>14}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Canada"=>1, "United States"=>4, "Germany"=>1, "Spain"=>1}, "group_count"=>0}

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• http://doi.org/10.1016/j.celrep.2012.12.003
• http://doi.org/10.1093/nar/gkx242
• http://doi.org/10.1016/j.tig.2011.04.002
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• http://doi.org/10.1074/jbc.M116.739375
• http://doi.org/10.1038/s41581-020-00359-2

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/447373"], "description"=>"<div><p>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 <em>S. cerevisiae</em> 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.</p></div>", "links"=>[], "tags"=>["pathway", "suppresses", "cryptic", "transcription"], "article_id"=>148164, "categories"=>["Genetics", "Molecular Biology"], "users"=>["Colin R. Lickwar", "Bhargavi Rao", "Andrey A. Shabalin", "Andrew B. Nobel", "Brian D. Strahl", "Jason D. Lieb"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0004886"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_Set2_Rpd3S_Pathway_Suppresses_Cryptic_Transcription_without_Regard_to_Gene_Length_or_Transcription_Frequency/148164", "title"=>"The Set2/Rpd3S Pathway Suppresses Cryptic Transcription without Regard to Gene Length or Transcription Frequency", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-03-19 02:16:04"}
• {"files"=>["https://ndownloader.figshare.com/files/904403"], "description"=>"<p>(A) YGL142C exhibits cryptic initiation in the set2<i>Δ</i> strain (red, <i>supF</i> 29.7), but not wild-type (blue). Plotted along the length of YGL142C are <i>z</i> scores of wild type (Wt) RNA raw probe intensity values (blue); <i>set2Δ</i> RNA/Wt RNA (red) and <i>set2Δ</i>/Wt ratios from Li et al. 2007 (green). The transition probe detected by our algorithm is marked by a dashed red line and red arrow. The solid lines represent the average <i>z</i> score for Wt (blue) and <i>set2</i><i>Δ</i>/Wt values (red) before and after the cryptic initiation event. This cryptic initiation event was confirmed by Northern blotting (not shown). (B) Genes identified as containing cryptic initiation sites according to our liberal (<i>supF</i> 3.0, 1193 genes) or conservative (<i>supF</i> 9.0, 429 genes) criteria were compared to the genes identified as containing a cryptic initiation event from Li et al. 2007 (1033 genes, orange). Shown at far right is the average intersection of 429 genes chosen at random with the Li et al set.</p>", "links"=>[], "tags"=>["cryptic", "initiation", "sites", "strains", "lacking"], "article_id"=>574857, "categories"=>["Genetics", "Molecular Biology"], "users"=>["Colin R. Lickwar", "Bhargavi Rao", "Andrey A. Shabalin", "Andrew B. Nobel", "Brian D. Strahl", "Jason D. Lieb"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0004886.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Detection_of_cryptic_initiation_sites_in_S_cerevisiae_strains_lacking_Set2_/574857", "title"=>"Detection of cryptic initiation sites in <i>S. cerevisiae</i> strains lacking Set2.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-03-19 01:20:57"}
• {"files"=>["https://ndownloader.figshare.com/files/904513"], "description"=>"<p>(A) The number of cryptic initiation events detected per base increases with gene length. Shown is the detection rate for five gene-length bins at conservative (<i>supF</i> 9, 801 transitions, blue) and liberal (<i>supF</i> 3, 1757 transitions, red) cutoffs. (B–C) Reducing the number of probes flanking a transition event causes statistical significance to decrease. Plotted along the length of YDR104C are <i>z</i> scores of <i>set2Δ</i> RNA/Wt RNA. The solid horizontal lines represent the average <i>z</i> score for the <i>set2</i><i>Δ</i>/Wt values (red) before and after the cryptic initiation event. The black solid and dashed vertical lines correspond to the number of probes required to achieve the <i>supF</i> 9 and <i>supF</i> 3 cutoffs respectively. Panel C plots the calculated <i>supF</i> values (y-axis) as a window centered on the detected transition shrinks, causing fewer probes to be available for transition detection (x-axis). The solid and dashed black lines call attention to the <i>supF</i> 9 and <i>supF</i> 3 cutoffs. (D–E) Same as B and C, but for YAL026C. (F) Detection of cryptic initiation sites using subgenes of uniform length eliminates the relationship between gene length and cryptic initiation frequency. Cryptic initiation rates for subgene analysis (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004886#s3\" target=\"_blank\">Methods</a>) using liberal (green; <i>supF</i> = 0.58, 2417 transitions), moderate (red; <i>supF</i> = 0.97, 1135 transitions), and conservative (blue; <i>supF</i> = 1.8, 364 transitions) cutoffs are plotted for different gene-length bins. (G) Random distribution of cryptic initiation events mimics the real distribution discovered after controlling ascertainment bias. Plot is the same as panel F, but transitions were randomly assigned to ORF probes (liberal; 2417 transitions, moderate; 1135 transitions, conservative; 364 transitions). Compare G and F. The slight downward trend in both plots may result from a slightly lower probe density in longer genes, which was not corrected for.</p>", "links"=>[], "tags"=>["initiation", "events"], "article_id"=>574972, "categories"=>["Genetics", "Molecular Biology"], "users"=>["Colin R. Lickwar", "Bhargavi Rao", "Andrey A. Shabalin", "Andrew B. Nobel", "Brian D. Strahl", "Jason D. Lieb"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0004886.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cryptic_initiation_events_occur_without_regard_to_gene_length_/574972", "title"=>"Cryptic initiation events occur without regard to gene length.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-03-19 01:22:52"}
• {"files"=>["https://ndownloader.figshare.com/files/904632"], "description"=>"<p>(A) Infrequently transcribed genes tend to be long. The average gene length for each transcription-rate bin is shown. (B) Without correcting for gene length, infrequently transcribed genes appear to have a higher rate of cryptic initiation. Genes were binned according to their transcription rate, and the cryptic initiation rate was determined for each bin. (C) Detection of cryptic initiation sites using subgenes of uniform length eliminates the inverse relationship between gene transcription frequency and cryptic initiation frequency. There may in fact be a trend toward more cryptic initiation in heavily transcribed genes. (D) Probe density cannot account for the observed relationship between transcription frequency and cryptic initiation frequency. Probe coverage is fairly uniform across gene transcription rate bins.</p>", "links"=>[], "tags"=>["initiation", "events", "transcriptional"], "article_id"=>575089, "categories"=>["Genetics", "Molecular Biology"], "users"=>["Colin R. Lickwar", "Bhargavi Rao", "Andrey A. Shabalin", "Andrew B. Nobel", "Brian D. Strahl", "Jason D. Lieb"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0004886.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cryptic_initiation_events_occur_without_regard_to_transcriptional_frequency_/575089", "title"=>"Cryptic initiation events occur without regard to transcriptional frequency.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-03-19 01:24:49"}

PMC Usage Stats | Further Information

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• {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"11"}

Relative Metric

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F1000Prime