GEO series

HIRA protects telomeres against R-loop-induced instability in ALT cancer cells [ATAC-seq]

GSE269268 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 12 samples Submitted 2024/10/21 Platform GPL30173

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 12 samples

What it is: ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism: Homo sapiens (human)
Samples: 12 samples: 12 samples, each with a distinct title — no replicated groupsGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: HIRA protects telomeres against R-loop-induced instability in ALT cancer cellsCell reports · 2024

Summary (written by the submitters)

Alterations to chromatin modifiers, such as the inactivating mutations in the ATRX-DAXX chromatin remodeling/histone H3.3 deposition complex, are implicated as drivers of the cancer-specific Alternative Lengthening of Telomeres (ALT) pathway. Prior studies revealed that HIRA adapts to compensate for ATRX-DAXX loss to sustain ALT cancer cell survival.

Read the full summary ↓

However, the specific mechanisms underlying HIRA’s ability to rescue telomeres from the consequences of ATRX-DAXX loss remain unclear. Here, using ATAC-seq and CUT&RUN, we demonstrate that HIRA-mediated deposition of new H3.3 is essential to maintain chromatin accessibility and to prevent the detrimental accumulation of nucleosome-free single-stranded DNA (ssDNA) at telomeres in ATRX-deficient ALT cancer cells. We provide evidence that the timely deposition of new H3.3 by HIRA and interacting partners UBN1 and UBN2 is crucial to prevent unwarranted TERRA R-loop formation and transcription-replication conflicts (TRCs) at telomeres. Furthermore, we determined that the delivery of H3.3 to telomeric chromatin by HIRA may link the phosphorylation of an H3.3-specific amino acid, serine 31, by Chk1 with mechanisms that promote productive ALT. Therefore, these studies identify a role for HIRA-mediated histone H3.3 deposition in TERRA R-loop homeostasis that we propose is essential for ensuring the survival of ALT cancer cells where the ATRX-DAXX complex is activated.

Published in

HIRA protects telomeres against R-loop-induced instability in ALT cancer cells

Lynskey ML, Brown EE, Bhargava R et al. · Cell reports 2024 · PMID 39509271 · doi:10.1016/j.celrep.2024.114964

This dataset

Open GSE269268 in finder → Find more human ChIP / ATAC / CUT&Tag datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE269268_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1120891 and SRA study SRP512278. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39509271) ↗

Study design

12 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 12 sample titles: 12 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM8311186 IMR90_KD_Rep1_ATACseq
GSM8311187 IMR90_KD_Rep2_ATACseq
GSM8311188 IMR90_KD_Rep3_ATACseq
GSM8311189 IMR90_HIRA_KD_Rep1_ATACseq
GSM8311190 IMR90_HIRA_KD_Rep2_ATACseq
GSM8311191 IMR90_HIRA_KD_Rep3_ATACseq
GSM8311192 IMR90_ATRX_KO_conKD_Rep1_ATACseq
GSM8311193 IMR90_ATRX_KO_conKD_Rep2_ATACseq
GSM8311194 IMR90_ATRX_KO_conKD_Rep3_ATACseq
GSM8311195 IMR90_ATRX_KO_HIRA_KD_Rep1_ATACseq
GSM8311196 IMR90_ATRX_KO_HIRA_KD_Rep2_ATACseq
GSM8311197 IMR90_ATRX_KO_HIRA_KD_Rep3_ATACseq

Datasets on a similar topic

GSE278751 A stem cell model identifies two alternative cell fates in CBFA2T3::GLIS2-driven acute megakaryoblastic leukemia initiation (Multiome scRNA-seq/scATAC-seq) 14 samples shares alt, atac-seq
GSE254185 Single-nuclei RNA/ATAC-seq of healthy and injured human kidney nephrectomy tissue 12 samples shares alt, atac-seq
GSE253893 PAX translocations remodel mitochondrial metabolism through altered leucine usage in rhabdomyosarcoma [Cut&Run] 28 samples shares alt
GSE279480 Longitudinally stable T cell and innate immune activity distinguish healthy adult immunotypes I 1021 samples shares alt
GSE299043 Multimodal profiling reveals tissue-directed signatures of human immune cells altered with age 654 samples shares alt
GSE271332 High-Throughput Transcriptomics Toxicity Assessment of Eleven Data-Poor Bisphenol A Alternatives 286 samples shares alt
GSE288172 Influence of NIPBL Knockdown-Induced Alterations in Cohesin Loop Extrusion on CTCF Loops, Enhancer-Promoter Connectivity, and PRC Domain Contacts During hESC Differentiation into Pancreatic Lineages 263 samples shares alt
GSE36701 Gene expression analysis of rectal mucosa in chronic irritable bowel syndrome (IBS) compared to healthy volunteers (HV) 221 samples shares alt

Search all human ChIP / ATAC / CUT&Tag datasets in GEO →

Share this dataset

Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.