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Motif distribution and DNA methylation underlie distinct Cdx2 binding during development and homeostasis

GSE253736 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 43 samples Submitted 2024/11/28 Platform GPL19057Platform GPL24676Platform GPL24247
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 43 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
43 samples: 18 conditions, mostly in duplicateGroups 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
Motif distribution and DNA methylation underlie distinct Cdx2 binding during development and homeostasisNature communications · 2025
Summary (written by the submitters)
Transcription factors guide tissue development by binding to developmental stage-specific targets and establishing an appropriate enhancer landscape. In turn, DNA and chromatin modifications direct the genomic binding of transcription factors. However, how transcription factors navigate chromatin features to selectively bind a small subset of all the possible genomic target loci remains poorly understood.
Read the full summary ↓
Here we show that Cdx2 - a lineage defining transcription factor that binds distinct targets in developing versus adult intestinal epithelial cells - has a preferential affinity for a non-canonical CpG-containing motif in vivo. A higher frequency of this motif at embryonic Cdx2 targets and methylated state of the CpG during development enables selective Cdx2 binding and activation of developmental enhancers and genes. In adult cells, demethylation at these enhancers prevents ectopic Cdx2 binding, instead directing Cdx2 to its canonical motif without a CpG. This shift in Cdx2 binding facilitates Ctcf and Hnf4 recruitment, establishing super-enhancers during development and homeostatic enhancers in adult cells, respectively. Induced DNA methylation in adult mouse epithelium or cultured cells recruits Cdx2 to developmental targets, promoting corecruitment of partner transcription factors. Thus, Cdx2’s differential CpG motif preferences enable it to navigate distinct DNA methylation profiles, activating genes specific to appropriate developmental stages.
Published in
Motif distribution and DNA methylation underlie distinct Cdx2 binding during development and homeostasis
Lorzadeh A, Ye G, Sharma S et al. · Nature communications 2025 · PMID 39843425 · doi:10.1038/s41467-025-56187-0
This dataset
Open GSE253736 in finder → Find more 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 GSE253736_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 PRJNA1066827 and SRA study SRP484800. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39843425) ↗
Study design
18 conditions, mostly in duplicate
Adult_H3K27me ×3 EedKO_H3K27me ×3 Adult_H3K36me ×2 EedKO_H3K36me ×2 EedKO ×2 E12.5_CDX2 ×2 E16.5_CDX2 ×2 E16.5_CTCF ×2 +15 more

Supports a between-group comparison across 38 samples.

How we read this: 18 replicated groups read from 43 sample titles; they account for 38 of them. 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

+ 3 more — browse all 43 samples with per-sample file links →

Datasets on a similar topic

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