GEO series
Chromatin-dependent motif syntax defines differentiation trajectories [ChIP-seq]
GSE272524
Mus musculus
Genome binding/occupancy profiling by high throughput sequencing
76 samples
Submitted 2025/08/07
Platform GPL17021Platform GPL24247Platform GPL19057
Summary
Transcription factors (TFs) recognizing DNA motifs within regulatory regions drive cell identity. Despite recent advances, their specificity remains incompletely understood. Here, we address this by contrasting two TFs, Neurogenin-2 (NGN2) and MyoD1, which recognize ubiquitous E-box motifs yet drive distinct cell fates toward neurons and muscles, respectively. Upon induction in mouse embryonic stem cells, we monitor binding across differentiation, employing an interpretable machine learning approach that integrates preexisting DNA accessibility. This reveals a chromatin-dependent motif syntax, delineating both common and factor-specific binding, validated by cellular and in vitro assays. Shared binding sites reside in open chromatin, locally influenced by nucleosomes. In contrast, factor-specific binding in closed chromatin involves NGN2 and MyoD1 acting as pioneer factors, influenced by motif variant frequencies, motif spacing, and interaction partners, which together account for subsequent lineage divergence. Transferring our methodology to other models demonstrates how a combination of opportunistic binding and context-specific chromatin-opening underpin TF specificity, driving differentiation trajectories.
Published in
Durdu S, Iskar M, Isbel L et al.
· Molecular cell 2025
· PMID 40780181
· doi:10.1016/j.molcel.2025.07.005
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE272524_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 76 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1137298 and SRA study SRP520744. Searching any of these in the dataset finder brings you back here.
Study design
6 conditions, mostly in triplicate
ChIPseq_GFP_6h ×6
ChIPseq_NGN2_6h ×3
ChIPseq_NGN2mut_6h ×3
ChIPseq_input_NGN2_6h ×3
ChIPseq_MYOD1_6h ×3
ChIPseq_GFP_24h ×2
ChIPseq_NGN2_ES6h ×1
ChIPseq_input_NGN2_ES6h ×1
+18 more
Supports a between-group comparison across 20 samples.
6 replicated groups read from the first 40 of 76 sample titles; they account for 20 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8403925 ChIPseq_NGN2_6h_1706
- GSM8403926 ChIPseq_NGN2mut_6h_1706
- GSM8403927 ChIPseq_GFP_6h_1706
- GSM8403928 ChIPseq_input_NGN2_6h_1706
- GSM8403929 ChIPseq_NGN2_6h_1848
- GSM8403930 ChIPseq_NGN2mut_6h_1848
- GSM8403931 ChIPseq_GFP_6h_1848
- GSM8403932 ChIPseq_input_NGN2_6h_1848
- GSM8403933 ChIPseq_NGN2_ES6h_1848
- GSM8403934 ChIPseq_input_NGN2_ES6h_1848
- GSM8403935 ChIPseq_NGN2_12h_1848
- GSM8403936 ChIPseq_NGN2mut_12h_1848
- GSM8403937 ChIPseq_GFP_12h_1848
- GSM8403938 ChIPseq_input_NGN2_12h_1848
- GSM8403939 ChIPseq_NGN2_ES12h_1848
- GSM8403940 ChIPseq_NGN2_24h_1848
- GSM8403941 ChIPseq_NGN2mut_24h_1848
- GSM8403942 ChIPseq_GFP_24h_1848
- GSM8403943 ChIPseq_input_NGN2_24h_1848
- GSM8403944 ChIPseq_NGN2_ES24h_1848
- GSM8403945 ChIPseq_NGN2_6h_1849
- GSM8403946 ChIPseq_NGN2mut_6h_1849
- GSM8403947 ChIPseq_GFP_6h_1849
- GSM8403948 ChIPseq_input_NGN2_6h_1849
- GSM8403949 ChIPseq_MYOD1_6h_2326
- GSM8403950 ChIPseq_MYOD1mut_6h_2326
- GSM8403951 ChIPseq_GFP_6h_2326
- GSM8403952 ChIPseq_MYOD1_6h_2007
- GSM8403953 ChIPseq_GFP_6h_2007
- GSM8403954 ChIPseq_input_MYOD1_6h_2007
- GSM8403955 ChIPseq_MYOD1_6h_2196
- GSM8403956 ChIPseq_GFP_6h_2196
- GSM8403957 ChIPseq_MYOD1_24h_2706
- GSM8403958 ChIPseq_MYOD1mut_24h_2706
- GSM8403959 ChIPseq_GFP_24h_2706
- GSM8403960 ChIPseq_MYOD1_48h_2706
- GSM8403961 ChIPseq_MYOD1mut_48h_2706
- GSM8403962 ChIPseq_GFP_48h_2706
- GSM8403963 ChIPseq_H3K27ac_NGN2_6h_r1_2052
- GSM8403964 ChIPseq_H3K27ac_NGN2_6h_r2_2052
+ 36 more — browse all 76 samples with per-sample file links →
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