GEO series

Alternative splicing of a chromatin modifier alters the transcriptional regulatory programs of embryonic stem cell maintenance and neuronal differentiation [ChIP-seq]

GSE241379 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 20 samples Submitted 2024/03/05 Platform GPL21493

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 20 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: Mus musculus (mouse)
Samples: 20 samples: 20 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: Alternative splicing of a chromatin modifier alters the transcriptional regulatory programs of stem cell maintenance and neuronal differentiationCell stem cell · 2024

Summary (written by the submitters)

Maintenance of embryonic stem cells (ESCs) and their differentiation to neuronal lineages requires complex genetic regulation of transcription, splicing, and translation, but the interconnections of these processes is not well understood. We found that the splicing regulator polypyrimidine tract binding protein 1 (PTBP1) alters the neuronal transcriptional program.

Read the full summary ↓

Transcripts for DPF2, a subunit of the BRG1/BRM-associated factor (BAF) chromatin remodeling complex, contain an additional exon (exon 7) in brain. This exon encodes a 14 amino acid insert in the C2H2-type zinc finger domain generating a longer DPF2-L isoform, compared to the canonical short DPF2-S isoform. We find that inclusion of exon 7 in Dpf2 mRNA is strongly inhibited by PTBP1, and loss PTBP1 switches expression from DPF2-S to DPF2-L early in neuronal differentiation. We created CRISPR/Cas9-mediated genome-edited cells that force expression of either DPF2-S or DPF2-L to examine the consequences of this switch in ESCs, in ESC-derived neural progenitor cells (NPCs), and in glutamatergic neurons (GNs). We found substantial changes in gene expression induced by DPF2-L in ESCs and by loss of this isoform in neurons. Chromatin immunoprecipitation in ESCs revealed that DPF2-S but not DPF2-L preferentially bound to genomic regions associated with the stem cell pluripotency transcription factors OCT4, SOX2, and NANOG. In NPC’s, DPF2-S preferentially bound to genomic regions co-occupied by the transcription factor NF1, while DPF2-L preferred sites bound by the CTC binding factor, CTCF. The correlation of DPF2 isoform binding with chromatin states identified by ChromHMM revealed that DPF2-S binds to sites enriched in enhancers, whereas DPF2-L-bound sites are enriched for promoters. Altogether, our study identifies a new neuronal BAF isoform that alters its functional targets, and demonstrates how splicing regulatory events during development elicit wide ranging impacts on chromatin organization and transcription.

Published in

Alternative splicing of a chromatin modifier alters the transcriptional regulatory programs of stem cell maintenance and neuronal differentiation

Nazim M, Lin CH, Feng AC et al. · Cell stem cell 2024 · PMID 38701759 · doi:10.1016/j.stem.2024.04.001

This dataset

Open GSE241379 in finder → Find more mouse 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 GSE241379_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 PRJNA1007778 and SRA study SRP456200. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38701759) ↗

Study design

20 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 20 sample titles: 20 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

GSM7727962 ESC_WT-1 (ChIP-seq rep-1)
GSM7727963 ESC_WT-2 (ChIP-seq rep-2)
GSM7727964 ESC_WT-3 (ChIP-seq rep-3)
GSM7727965 ESC_E7KO-1 (ChIP-seq rep-1)
GSM7727966 ESC_E7KO-2 (ChIP-seq rep-2)
GSM7727967 ESC_E7KO-3 (ChIP-seq rep-3)
GSM7727968 ESC_E7KI-1 (ChIP-seq rep-1)
GSM7727969 ESC_E7KI-2 (ChIP-seq rep-2)
GSM7727970 ESC_E7KI-3 (ChIP-seq rep-3)
GSM7727971 ESC_input
GSM7727972 NPC_WT-1 (ChIP-seq rep-1)
GSM7727973 NPC_WT-2 (ChIP-seq rep-2)
GSM7727974 NPC_WT-3 (ChIP-seq rep-3)
GSM7727975 NPC_E7KO-1 (ChIP-seq rep-1)
GSM7727976 NPC_E7KO-2 (ChIP-seq rep-2)
GSM7727977 NPC_E7KO-3 (ChIP-seq rep-3)
GSM7727978 NPC_E7KI-1 (ChIP-seq rep-1)
GSM7727979 NPC_E7KI-2 (ChIP-seq rep-2)
GSM7727980 NPC_E7KI-3 (ChIP-seq rep-3)
GSM7727981 NPC_input

Datasets on a similar topic

GSE268172 Stable maintenance of MERVL-positive embryonic stem cells reveals sustained transcriptional programs and enhancer remodeling 45 samples shares maintenance, embryonic, programs
GSE322558 Physiologic variation in sperm miRNAs tunes embryonic gene regulatory programs and developmental outcomes 622 samples shares regulatory, embryonic, programs
GSE267882 Foxp3 and BATF cooperatively direct cis-regulatory programs and gene expression for effector Treg cell differentiation [ChIP-Seq] 34 samples shares regulatory, programs
GSE283483 Novel environment exposure drives temporally defined and region-specific chromatin accessibility and gene expression programs in the hippocampus 160 samples shares chromatin, programs
GSE318069 eIF4G2-mediated Translation Initiation of Histone Modifiers is Essential for Intestinal Stem Cell Maintenance and Differentiation 145 samples shares maintenance, modifier
GSE290224 Intermittent Fasting Reprograms Chromatin Accessibility to Modulate Gene Expression in Brain and Muscle 96 samples shares chromatin, programs
GSE288605 Context-Dependent and Gene-Specific Role of Chromatin Architecture Mediated by Histone Modifiers and Loop-extrusion Machinery 96 samples shares chromatin, modifier
GSE342312 T-bet and Runx3 orchestrate effector CD8 T cell differentiation and lineage fidelity through cooperative and distinct chromatin regulatory mechanisms [Multi-omics] 40 samples shares regulatory, chromatin

Search all mouse 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.