GEO series

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

GSE253726 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 12 samples Submitted 2024/11/29 Platform GPL24247

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 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: Mus musculus (mouse)
Samples: 12 samples: 3 × Adult_H3K27me vs 3 × EedKO_H3K27me vs 2 × Adult_H3K36me vs 2 × EedKO_H3K36meGroups 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)

Precise spatiotemporal and cell type-specific gene expression is essential for proper tissue development and function. Transcription factors (TFs) guide this process by binding to developmental stage-specific targets and establishing an appropriate enhancer landscape. DNA and chromatin modifications form barriers to the genomic binding of TFs, however, the details of how TFs navigate various chromatin features and selectively bind a small portion of the millions of possible genomic target loci remain unknown.

Read the full summary ↓

Here we show that Cdx2, a pioneer TF that binds distinct targets in developing and adult intestinal epithelial cells, has a preferential affinity to a non-canonical CpG-containing motif in vivo. A higher frequency of this motif at the embryonic and fetal target loci of Cdx2 and the methylated state of the CpG particularly during development allows its selective binding and activation of developmental enhancers and linked genes. Conversely, demethylation at these enhancers prohibits ectopic Cdx2 binding in adult cells, where Cdx2 binds the canonical motif without a CpG. This distinct Cdx2 binding allows corecruitment of Ctcf and Hnf4 facilitating the establishment of intestinal superenhancers during development and enhancers activating adult tissue functions, respectively. Induced gain of DNA methylation in the adult epithelium in vivo or in cultured cells causes recruitment of Cdx2 to the developmental target loci and cobinding of the partner TFs. Our results demonstrate that the distinct propensities of Cdx2 to bind motifs with and without CpGs and the divergent distribution of these motifs at developmental and adult target sites allow Cdx2 to navigate distinct DNA methylation profiles and activate cell type-specific enhancers and genes.

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 GSE253726 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 GSE253726_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 PRJNA1066832 and SRA study SRP484779. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39843425) ↗

Study design

3 × Adult_H3K27me vs 3 × EedKO_H3K27me vs 2 × Adult_H3K36me vs 2 × EedKO_H3K36me

Supports a between-group comparison across 10 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 10 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

GSM8027019 Adult_H3K27me1 Adult_H3K27me
GSM8027020 Adult_H3K27me2 Adult_H3K27me
GSM8027021 Adult_H3K27me3 Adult_H3K27me
GSM8027022 Adult_H3K36me2 Adult_H3K36me
GSM8027023 Adult_H3K36me3 Adult_H3K36me
GSM8027024 Adult_H2AK119Ub
GSM8027025 EedKO_H3K27me1 EedKO_H3K27me
GSM8027026 EedKO_H3K27me2 EedKO_H3K27me
GSM8027027 EedKO_H3K27me3 EedKO_H3K27me
GSM8027028 EedKO_H3K36me2 EedKO_H3K36me
GSM8027029 EedKO_H3K36me3 EedKO_H3K36me
GSM8027030 EedKO_H2AK119Ub

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