title: Simultaneous characterization of sense and antisense genomic processes by the double-stranded hidden Markov model.
abstract: Hidden Markov models (HMMs) have been extensively used to dissect the genome into functionally distinct regions using data such as RNA expression or DNA binding measurements. It is a challenge to disentangle processes occurring on complementary strands of the same genomic region. We present the double-stranded HMM (dsHMM), a model for the strand-specific analysis of genomic processes. We applied dsHMM to yeast using strand specific transcription data, nucleosome data, and protein binding data for a set of 11 factors associated with the regulation of transcription.The resulting annotation recovers the mRNA transcription cycle (initiation, elongation, termination) while correctly predicting strand-specificity and directionality of the transcription process. We find that pre-initiation complex formation is an essentially undirected process, giving rise to a large number of bidirectional promoters and to pervasive antisense transcription. Notably, 12% of all transcriptionally active positions showed simultaneous activity on both strands. Furthermore, dsHMM reveals that antisense transcription is specifically suppressed by Nrd1, a yeast termination factor.
authors.affiliation: Gene Center Munich and Department of Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Straße 25, 81377 Munich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Glas
authors.affiliation: Department of Plant Breeding and Genetics, Max Planck Institute for Plant Breeding Research, Carl-von-Linné-Weg 10, 50829 Cologne, Germany Institute for Genetics, University of Cologne, Zülpicher Str. 47b, 50674 Cologne, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dümcke
authors.affiliation: Gene Center Munich and Department of Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Straße 25, 81377 Munich, Germany Department of Plant Breeding and Genetics, Max Planck Institute for Plant Breeding Research, Carl-von-Linné-Weg 10, 50829 Cologne, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Zacher
authors.affiliation: Institute for Genetics, University of Cologne, Zülpicher Str. 47b, 50674 Cologne, Germany.
authors.forename: Don
authors.initials: D
authors.lastname: Poron
authors.affiliation: Gene Center Munich and Department of Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Straße 25, 81377 Munich, Germany.
authors.forename: Julien
authors.initials: J
authors.lastname: Gagneur
authors.affiliation: Gene Center Munich and Department of Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Straße 25, 81377 Munich, Germany Department of Plant Breeding and Genetics, Max Planck Institute for Plant Breeding Research, Carl-von-Linné-Weg 10, 50829 Cologne, Germany Institute for Genetics, University of Cologne, Zülpicher Str. 47b, 50674 Cologne, Germany tresch@genzentrum.lmu.de.
authors.forename: Achim
authors.initials: A
authors.lastname: Tresch
mesh_terms: D004247:DNA / Q000235:genetics* / Q000378:metabolism; D004271:DNA, Fungal / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D023281:Genomics; D008390:Markov Chains; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004271:DNA, Fungal; C491211:NRD1 protein, S cerevisiae; D009707:Nucleosomes; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D004247:DNA