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G-quadruplex folding in Xist RNA antagonizes PRC2 activity for step-wise regulation of X-chromosome inactivation

ABSTRACT: G-quadruplex folding in Xist RNA antagonizes PRC2 activity for step-wise regulation of X-chromosome inactivation

PROVIDER: PRJNA906999 | ENA |

REPOSITORIES: ENA

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G-quadruplex folding in Xist RNA antagonizes PRC2 activity for step-wise regulation of X-chromosome inactivation

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Promoter G-quadruplex folding precedes transcription and is controlled by chromatin

Project description:Four stranded DNA G-quadruplex (G4) structures are common features of the human genome that are primarily found in active promoters associated with elevated transcription. Here, we explore the relationship between the folding of G4s in promoters, transcription and chromatin state. Transcriptional inhibition by DRB or by triptolide reveals that promoter G4 formation, as assessed G4 ChIP-seq, is not reliant on transcriptional activity. Establishing a link between G4 formation and chromatin accessibility, we demonstrate that chromatin compaction leads to loss of promoter G4s accompanied by a corresponding loss of RNA polymerase II (Pol II). Furthermore, pre-treatment of cells with a G4-stabilising ligand can mitigate Pol II loss at promoters induced by chromatin compaction. Overall, our findings show that G4 formation is fostered in accessible chromatin and does not require active transcription. Furthermore, our findings suggest that G4s have a role to recruit Pol II to promote transcription.

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G-Quadruplex structures are stable and detectable in human genomic DNA.

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