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

ABSTRACT: We analyze G-quadruplex enrichment in ATRX KO mESC

ORGANISM(S): Mus musculus

PROVIDER: GSE171461 | GEO | 2021/05/17

REPOSITORIES: GEO

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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 [EdU-seq]

Project description:We analyze the contribution of ATRX and DAXX to G-quadruplex DNA replication in mESC

2021-05-17 | GSE151056 | GEO

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

Project description:We analyze ATRX enrichment in ATRX-GFP and FACT subunits KD mESC

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

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

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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

ATRX promotes heterochromatin formation to protect cells from G-quadruplex DNA-mediated stress

Project description:ATRX promotes heterochromatin formation to protect cells from G-quadruplex DNA-mediated stress

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G-quadruplex stabilizer CX-5461 effectively combines with ionizing radiation to selectively target ATRX-deficient malignant glioma [CUT&Tag]

Project description:Mutational inactivation of ?-thalassaemia/mental retardation X-linked (ATRX) represents a defining molecular feature in large subsets of adult and pediatric malignant glioma. ATRX deficiency gives rise to abnormal G-quadruplex (G4) DNA secondary structures at GC-rich regions of the genome, altering chromatin accessibility and enhancing DNA damage. Building on earlier work, we sought to assess the extent to which pharmacological G4 stabilization selectively enhances DNA damage and cell death in preclinical models of ATRX-deficient glioma. To investigate the effect of G4 stabilization on histone variant H3.3 deposition on the genome, we treated patient-derived glioma stem cells (GSCs) with G4 stabilizer CX-5461 and performed cleavage under targets and tagmentation (CUT&Tag) for H3.3. Our analyses show that G4 stabilizer CX-541 disrupts H3.3 deposition in ATRX-deficient GSCs and likely enhances replication stress and DNA damage.

2024-03-18 | GSE261562 | GEO

ATRX promotes heterochromatin formation to protect cells from G-quadruplex DNA-mediated stress.

Project description:ATRX is a tumor suppressor that has been associated with protection from DNA replication stress, purportedly through resolution of difficult-to-replicate G-quadruplex (G4) DNA structures. While several studies demonstrate that loss of ATRX sensitizes cells to chemical stabilizers of G4 structures, the molecular function of ATRX at G4 regions during replication remains unknown. Here, we demonstrate that ATRX associates with a number of the MCM replication complex subunits and that loss of ATRX leads to G4 structure accumulation at newly synthesized DNA. We show that both the helicase domain of ATRX and its H3.3 chaperone function are required to protect cells from G4-induced replicative stress. Furthermore, these activities are upstream of heterochromatin formation mediated by the histone methyltransferase, ESET, which is the critical molecular event that protects cells from G4-mediated stress. In support, tumors carrying mutations in either ATRX or ESET show increased mutation burden at G4-enriched DNA sequences. Overall, our study provides new insights into mechanisms by which ATRX promotes genome stability with important implications for understanding impacts of its loss on human disease.

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

Project description:ATRX promotes heterochromatin formation to protect cells from G-quadruplex DNA-mediated stress [ChIP-Seq]

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

Project description:ATRX promotes heterochromatin formation to protect cells from G-quadruplex DNA-mediated stress [EdU-seq]

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