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TERRA regulates DNA G-quadruplex formation and ATRX loading on chromatin

ABSTRACT: TERRA regulates DNA G-quadruplex formation and ATRX loading on chromatin

PROVIDER: PRJNA798772 | ENA |

REPOSITORIES: ENA

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TERRA regulates DNA G-quadruplex formation and ATRX loading on chromatin

Project description:The genome consists of non-B-DNA structures such as G-quadruplexes (G4) that are involved in the regulation of genome stability and transcription. Telomeric-repeat containing RNA (TERRA) is capable of folding into G-quadruplex and interacting with chromatin remodeler ATRX. Here we show that TERRA modulates ATRX occupancy on repetitive sequences and over genes, and maintains DNA G-quadruplex structures at TERRA target and non-target sites in mouse embryonic stem cells. TERRA prevents ATRX from binding to subtelomeric regions and represses H3K9me3 formation. G4 ChIP-seq reveals that G4 abundance decreases at accessible chromatin regions, particularly at transcription start sites (TSS) after TERRA depletion; such G4 reduction at TSS is associated with elevated ATRX occupancy and differentially expressed genes. Loss of ATRX alleviates the effect of gene repression caused by TERRA depletion. Immunostaining analyses demonstrate that knockdown of TERRA diminishes DNA G4 signals, whereas silencing ATRX elevates G4 formation. Our results uncover an epigenetic regulation by TERRA that sequesters ATRX and preserves DNA G4 structures.

2022-11-09 | GSE194038 | GEO

TERRA RNA antagonizes ATRX and protects telomeres

Project description:Through an integration of genomic and proteomic approaches to advance understanding of long noncoding RNAs, we investigate the function of the telomeric transcript, TERRA. By identifying thousands of TERRA target sites in the mouse genome, we demonstrate that TERRA can bind both in cis to telomeres and in trans to genic targets. We then define a large network of interacting proteins, including epigenetic factors, telomeric proteins, and the RNA helicase, ATRX. TERRA and ATRX share hundreds of target genes and are functionally antagonistic at these loci: whereas TERRA activates, ATRX represses gene expression. At telomeres, TERRA competes with telomeric DNA for ATRX binding, suppresses ATRX localization, and ensures telomeric stability. Depleting TERRA increases telomerase activity and induces telomeric pathologies, including formation of telomere-induced DNA damage foci and loss or duplication of telomeric sequences. We conclude that TERRA functions as an epigenomic modulator in trans and as an essential regulator of telomeres in cis.

2017-06-29 | GSE79180 | GEO

ATRX promotes heterochromatin formation to protect cells from G-quadruplex DNA-mediated stress [ATAC-Seq]

Project description:We analyze the contribution of ATRX, DAXX and HIRA to the chromatin accessibility at G-quadruplex in mESC We analyze the contribution of ATRX and ESET to the chromatin accessibility at G-quadruplex in mESC

2021-05-17 | GSE151053 | GEO

ATRX promotes heterochromatin formation to protect cells from G-quadruplex DNA-mediated stress [CUT&Tag]

Project description:We analyze G-quadruplex enrichment in ATRX KO mESC

2021-05-17 | GSE171461 | GEO