Project description: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.

| S-EPMC6735678 | biostudies-literature

PTEN modulates gene transcription by redistributing genome-wide RNA polymerase II occupancy

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-06-04 | GSE124659 | GEO

G+C content of transcribed sequence modulates DSIF-assisted DNA occupancy by RNA polymerase II

Project description:G+C content of transcribed sequence modulates DSIF-assisted DNA occupancy by RNA polymerase II

| PRJNA716652 | ENA

G+C content of transcribed sequence modulates DSIF-assisted DNA occupancy by RNA polymerase II [ChIP-seq]

Project description:G+C content of transcribed sequence modulates DSIF-assisted DNA occupancy by RNA polymerase II [ChIP-seq]

| PRJNA716629 | ENA

G+C content of transcribed sequence modulates DSIF-assisted DNA occupancy by RNA polymerase II [RNA-seq]

Project description:G+C content of transcribed sequence modulates DSIF-assisted DNA occupancy by RNA polymerase II [RNA-seq]

| PRJNA716749 | ENA

PTEN interacts with the transcription machinery on chromatin and regulates RNA polymerase II-mediated transcription [Affymetrix]

Project description:We demonstrate that PTEN interacts with the transcription machinery. Using ChIP-seq, we show that PTEN co-localizes with RNAPII and binds to chromatin in promoter and putative enhancer regions. We further show that loss of PTEN affects RNAPII occupancy in gene bodies and correlates with gene expression changes. Loss of PTEN also increased cells’ sensitivity to transcription inhibition via small molecules.

2019-04-03 | GSE120472 | GEO

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