GEO series

Effect of ASCL1 phosphorylation status on chromatin binding and target regulation in neuroblastoma

GSE153823 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 52 samples Submitted 2021/03/15 Platform GPL11154

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 52 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)
Topic: NeuroblastomaThis series is part of our curated briefing on it.
Samples: 52 samples
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.

Summary (written by the submitters)

ASCL1, a basic helix-loop-helix family transcription factor, is a master regulator of developmental neurogenesis and a crucial component of transcription factor cocktails that can convert heterologous cell types such as fibroblasts into neurons. The ability of ASCL1 to drive neuronal differentiation is controlled by multi-site phosphorylation but how this modification controls the genome-wide transcriptional activity of ASCL1 is unknown.

Read the full summary ↓

Using human neuroblastoma cells that maintain a rapidly dividing neuroblastic phenotype yet retain the ability to undergo differentiation as a model system, we find that phosphorylation of ASCL1 has limited effect on target gene promoter association, but predominantly regulates its binding to a subset of distal enhancer regions, resulting in extensive differences in target control by activation, as well as direct and indirect gene repression. These genome-wide analyses reveal how post-translational modification of ASCL1 can change its structure and function, driving it to differential regulatory elements to change cell fate, and controlling ASCL1’s activity as a master transcription regulator of neurogenesis. Using functional mutational and pharmacological approaches, we find that preventing CDK-dependent phosphorylation of ASCL1 in neuroblastoma cells results in co-ordinated suppression of the MYC-driven core circuit supporting neuroblast identity and proliferation, while simultaneously activating a gene programme driving neuronal differentiation. Thus, we show targeting the post-translational modification of a key developmental regulator can re-engage a latent genome-wide programme forcing mitotic exit and differentiation in cancer cells.

This dataset

Open GSE153823 in finder → Find more human RNA-seq datasets → Neuroblastoma landscape →

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 GSE153823_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 PRJNA644293 and SRA study SRP270228. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 33046535) ↗

Samples in this study

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+ 52 more — browse all 52 samples with per-sample file links →

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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.