RNA polymerase II pausing can be retained or acquired during activation of genes involved in the epithelial to mesenchymal transition
| Autor: | Oscar Nnoli, Jessica A. Warns, Kris Zarns, Bradley Jokinen, Sergei Nechaev, Ata Abbas, Ann Samarakkody, Adam Scheidegger, Brooke Kubat, Archana Dhasarathy |
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| Rok vydání: | 2015 |
| Předmět: |
Transcriptional Activation
Epithelial-Mesenchymal Transition Immunoprecipitation DNA polymerase II RNA polymerase II SNAI1 Gene 03 medical and health sciences 0302 clinical medicine Genetics Humans HSP70 Heat-Shock Proteins Promoter Regions Genetic Gene 030304 developmental biology Regulation of gene expression 0303 health sciences biology Gene regulation Chromatin and Epigenetics Molecular biology Chromatin 030220 oncology & carcinogenesis SNAI1 MCF-7 Cells biology.protein RNA Polymerase II Snail Family Transcription Factors Transcription Factors |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkv263 |
| Popis: | Promoter-proximal RNA polymerase II (Pol II) pausing is implicated in the regulation of gene transcription. However, the mechanisms of pausing including its dynamics during transcriptional responses remain to be fully understood. We performed global analysis of short capped RNAs and Pol II Chromatin Immunoprecipitation sequencing in MCF-7 breast cancer cells to map Pol II pausing across the genome, and used permanganate footprinting to specifically follow pausing during transcriptional activation of several genes involved in the epithelial to mesenchymal transition (EMT). We find that the gene for EMT master regulator Snail (SNAI1), but not Slug (SNAI2), shows evidence of Pol II pausing before activation. Transcriptional activation of the paused SNAI1 gene is accompanied by a further increase in Pol II pausing signal, whereas activation of non-paused SNAI2 gene results in the acquisition of a typical pausing signature. The increase in pausing signal reflects increased transcription initiation without changes in Pol II pausing. Activation of the heat shock HSP70 gene involves pausing release that speeds up Pol II turnover, but does not change pausing location. We suggest that Pol II pausing is retained during transcriptional activation and can further undergo regulated release in a signal-specific manner. |
| Databáze: | OpenAIRE |
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