PTEN modulates gene transcription by redistributing genome-wide RNA polymerase II occupancy
| العنوان: | PTEN modulates gene transcription by redistributing genome-wide RNA polymerase II occupancy |
|---|---|
| المؤلفون: | Todd Romigh, Ata Abbas, Roshan Padmanabhan, Charis Eng |
| المصدر: | Human Molecular Genetics |
| بيانات النشر: | Oxford University Press (OUP), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Transcription, Genetic, RNA Splicing, DNA polymerase II, RNA polymerase II, Biology, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, Genetics, Transcriptional regulation, Humans, PTEN, Tensin, Negative elongation factor, Promoter Regions, Genetic, P-TEFb, Molecular Biology, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Gene Expression Profiling, PTEN Phosphohydrolase, General Medicine, DSIF, Cell biology, Gene Expression Regulation, 030220 oncology & carcinogenesis, biology.protein, RNA Polymerase II, General Article, Transcriptome, Protein Binding |
| الوصف: | Control of gene expression is one of the most complex yet continuous physiological processes impacting cellular homeostasis. RNA polymerase II (Pol II) transcription is tightly regulated at promoter-proximal regions by intricate dynamic processes including Pol II pausing, release into elongation and premature termination. Pol II pausing is a phenomenon where Pol II complex pauses within 30–60 nucleotides after initiating the transcription. Negative elongation factor (NELF) and DRB sensitivity inducing factor (DSIF) contribute in the establishment of Pol II pausing, and positive transcription elongation factor b releases (P-TEFb) paused complex after phosphorylating DSIF that leads to dissociation of NELF. Pol II pausing is observed in most expressed genes across the metazoan. The precise role of Pol II pausing is not well understood; however, it’s required for integration of signals for gene regulation. In the present study, we investigated the role of phosphatase and tensin homolog (PTEN) in genome-wide transcriptional regulation using PTEN overexpression and PTEN knock-down models. Here we identify that PTEN alters the expression of hundreds of genes, and its restoration establishes genome-wide Pol II promoter-proximal pausing in PTEN null cells. Furthermore, PTEN re-distributes Pol II occupancy across the genome and possibly impacts Pol II pause duration, release and elongation rate in order to enable precise gene regulation at the genome-wide scale. Our observations demonstrate an imperative role of PTEN in global transcriptional regulation that will provide a new direction to understand PTEN-associated pathologies and its management. |
| تدمد: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/ddz112 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f50d9af8b0ec1a0eb3f4cdd086b3ae38 https://doi.org/10.1093/hmg/ddz112 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f50d9af8b0ec1a0eb3f4cdd086b3ae38 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602083 09646906 |
|---|---|
| DOI: | 10.1093/hmg/ddz112 |