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ATRX loss predicts poor outcomes and reveals a therapeutic vulnerability to TEAD inhibition in soft tissue sarcomas -- ATAC

ABSTRACT: ATRX is an ATP-dependent chromatin remodeler frequently altered in sarcomas and plays an important role in maintaining chromatin organization and transcriptional regulation. Loss of ATRX is associated with aggressive tumor behavior, but the chromatin regulatory mechanisms underlying ATRX-deficient sarcomas remain incompletely understood. In this study, we investigated changes in chromatin accessibility associated with ATRX loss in sarcoma models. We performed ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) to characterize genome-wide accessible chromatin landscapes in ATRX-deficient and control sarcoma cells. Our analyses identified widespread alterations in chromatin accessibility and chromatin de-repression following ATRX loss, with differential accessible regions enriched for transcription factor motifs. These ATAC-seq data provide genome-wide profiles of accessible chromatin and support investigation of ATRX-dependent regulatory elements and transcriptional programs in sarcoma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE346344 | GEO | 2026/09/21

REPOSITORIES: GEO

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ATRX loss predicts poor outcomes and reveals a therapeutic vulnerability to TEAD inhibition in soft tissue sarcomas -- RNA

Project description:ATRX is an ATP-dependent chromatin remodeler frequently altered in sarcomas and is involved in the maintenance of heterochromatin and transcriptional regulation. Loss of ATRX is associated with aggressive tumor behavior, but the transcriptional mechanisms underlying ATRX-deficient sarcomas remain incompletely understood. In this study, we performed bulk RNA sequencing (RNA-seq) across sarcoma cell lines and genetically engineered cell models with different ATRX backgrounds to characterize transcriptional changes associated with ATRX loss. The dataset includes leiomyosarcoma and liposarcoma cell lines as well as engineered human fibroblast and uterine smooth muscle cell models with perturbations of ATRX and related tumor suppressor genes. Comparative transcriptomic analyses were used to identify ATRX-dependent gene expression programs and transcriptional regulatory pathways. These RNA-seq data complement chromatin accessibility and chromatin profiling experiments and provide a transcriptional framework for understanding how ATRX loss alters regulatory programs in sarcoma.

2026-09-21 | GSE346694 | GEO

ATRX loss predicts poor outcomes and reveals a therapeutic vulnerability to TEAD inhibition in soft tissue sarcomas -- CUT&RUN v2

Project description:ATRX is an ATP-dependent chromatin remodeler frequently altered in sarcomas and is involved in maintaining heterochromatin and transcriptional regulation. Loss of ATRX is associated with aggressive tumor behavior, but the transcriptional regulatory mechanisms underlying ATRX-deficient sarcomas remain incompletely understood. In this study, we investigated chromatin and transcription factor regulatory changes associated with ATRX loss in sarcoma models. Our analyses identified chromatin de-repression following ATRX loss and enrichment of transcription factor motifs, including PRDM4 and NFIX. To characterize the genomic regulatory programs associated with these transcription factors, we performed CUT&RUN profiling to map transcription factor occupancy in sarcoma cells. These data provide genome-wide profiles of transcription factor binding and support investigation of the regulatory mechanisms associated with ATRX loss in sarcoma.

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ATRX loss predicts poor outcomes and reveals a therapeutic vulnerability to TEAD inhibition in soft tissue sarcomas

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