title: RNA polymerase II pausing as a context-dependent reader of the genome.
abstract: The RNA polymerase II (Pol II) transcribes all mRNA genes in eukaryotes and is among the most highly regulated enzymes in the cell. The classic model of mRNA gene regulation involves recruitment of the RNA polymerase to gene promoters in response to environmental signals. Higher eukaryotes have an additional ability to generate multiple cell types. This extra level of regulation enables each cell to interpret the same genome by committing to one of the many possible transcription programs and executing it in a precise and robust manner. Whereas multiple mechanisms are implicated in cell type-specific transcriptional regulation, how one genome can give rise to distinct transcriptional programs and what mechanisms activate and maintain the appropriate program in each cell remains unclear. This review focuses on the process of promoter-proximal Pol II pausing during early transcription elongation as a key step in context-dependent interpretation of the metazoan genome. We highlight aspects of promoter-proximal Pol II pausing, including its interplay with epigenetic mechanisms, that may enable cell type-specific regulation, and emphasize some of the pertinent questions that remain unanswered and open for investigation.
authors.affiliation: Department of Basic Sciences, University of North Dakota School of Medicine, Grand Forks, ND 58201, USA.|Department of Basic Sciences, University of North Dakota School of Medicine, Grand Forks, ND 58201, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Scheidegger
authors.affiliation: Department of Basic Sciences, University of North Dakota School of Medicine, Grand Forks, ND 58201, USA.|Department of Basic Sciences, University of North Dakota School of Medicine, Grand Forks, ND 58201, USA.
authors.forename: Sergei
authors.initials: S
authors.lastname: Nechaev
mesh_terms: D001483:Base Sequence; D002843:Chromatin / Q000378:metabolism; D044127:Epigenesis, Genetic; D016678:Genome; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D058727:RNA, Small Untranslated / Q000378:metabolism; D061805:Transcription Elongation, Genetic; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D002843:Chromatin; D012333:RNA, Messenger; D058727:RNA, Small Untranslated; D014157:Transcription Factors; C118437:negative elongation factor; D042925:Positive Transcriptional Elongation Factor B; D012319:RNA Polymerase II
keywords: Pol II; RNA polymerase pausing; epigenetics; gene regulation; pause de l’ARN polymérase II; régulation génique; transcription; épigénétique