GEO series
A core transcriptional regulatory circuitry controls super-enhancer-driven activation of LGR5 in colorectal cancer: ChIP-seq
GSE292300
Homo sapiens; Mus musculus
Genome binding/occupancy profiling by high throughput sequencing
76 samples
Submitted 2026/05/17
Platform GPL28038Platform GPL28457
Summary
The core transcriptional regulatory program governed by a small set of master transcription factors is pivotal for establishing context-specific cellular features, as has been elegantly illustrated in embryonic stem cells. Here, we reported an uncharted role of master transcription factor MYC in actively regulating cancer-type specific super-enhancer (SE) activity, and identified a core transcriptional regulatory circuitry consisting of MYC, ETS2, and FOXP1 in colorectal cancer (CRC). MYC/ETS2/FOXP1 bound to their own SEs and the SEs of other circuitry factors, thereby rapidly amplifying transcriptional effects upon activation. The majority of SEs were co-occupied by all three circuitry factors, and acute perturbation of the circuitry factors severely and selectively repressed a series of SE-controlled genes. Furthermore, there was functional inter-dependency between the circuitry and BRD4 in regulating SE-driven transcription, and targeting the circuitry factors sensitized CRC cells to BET inhibition. Notably, the key stemness gene LGR5 was activated by a circuitry-controlled distal SE in CRC, which was one of the most significantly gained tumor-specific SEs and was required for establishing CRC liver metastases. Lgr5 transcription in intestinal stem cells (ISCs) was likewise sustained by a Myc-regulated SE. Depletion of Myc in murine ISCs led to shrink of Lgr5-positive cell population, and impaired the renewal capacity of ISCs and intestinal epithelium integrity. Collectively, our study unveiled a core transcriptional regulatory module in CRC, advanced current understanding of MYC in transcription regulation, and provided mechanistic explanation for LGR5 overexpression in cancer. These findings may pave the way for precisely targeting detrimental transcription events in CRC therapy.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE292300_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 PRJNA1237848 and SRA study SRP571361. Searching any of these in the dataset finder brings you back here.
Study design
36 conditions, each sampled once — no replicated groups
HT29_MYC_AID_Ctrl_H3K27ac ×2
HT29_MYC_AID_IAA_H3K27ac ×2
HT29_MYC_AID_Ctrl_BRD4 ×2
HT29_MYC_AID_IAA_BRD4 ×2
Read from the first 40 of 76 sample titles: 36 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8855721 HT29_MYC_AID_Ctrl_input
- GSM8855722 HT29_MYC_AID_IAA_input
- GSM8855723 HT29_MYC_AID_Ctrl_H3K27ac_rep2
- GSM8855724 HT29_MYC_AID_IAA_H3K27ac_rep2
- GSM8855725 HT29_MYC_AID_Ctrl_MYC_rep1
- GSM8855726 HT29_MYC_AID_IAA_MYC_rep1
- GSM8855727 HT29_MYC_AID_Ctrl_TFIIB
- GSM8855728 HT29_MYC_AID_IAA_TFIIB
- GSM8855729 HT29_MYC_AID_IAA_0_min_MYC
- GSM8855730 HT29_MYC_AID_IAA_15_min_MYC
- GSM8855731 HT29_MYC_AID_IAA_60_min_MYC
- GSM8855732 HT29_MYC_AID_IAA_180_min_MYC
- GSM8855733 HT29_MYC_AID_Ctrl_KAT2A
- GSM8855734 HT29_MYC_AID_IAA_KAT2A
- GSM8855735 HT29_MYC_AID_Ctrl_H3K27ac
- GSM8855736 HT29_MYC_AID_IAA_H3K27ac
- GSM8855737 HT29_MYC_AID_Ctrl_H3K9ac
- GSM8855738 HT29_MYC_AID_IAA_H3K9ac
- GSM8855739 HT29_MYC_AID_IAA_0_min_RPB1
- GSM8855740 HT29_MYC_AID_IAA_15_min_RPB1
- GSM8855741 HT29_MYC_AID_IAA_60_min_RPB1
- GSM8855742 HT29_MYC_AID_IAA_180_min_RPB1
- GSM8855743 HT29_Vehicle_BRD4
- GSM8855744 HT29_KJPry9_BRD4
- GSM8855745 HT29_Omomyc_Vehicle_BRD4
- GSM8855746 HT29_Omomyc_dox_BRD4
- GSM8855747 HT29_BRD4
- GSM8855748 HT29_MYC_AID_Ctrl_BRD4_rep1
- GSM8855749 HT29_MYC_AID_IAA_BRD4_rep1
- GSM8855750 HT29_MYC_AID_Ctrl_FOXP1
- GSM8855751 HT29_MYC_AID_IAA_FOXP1
- GSM8855752 HT29_MYC_AID_Ctrl_p300
- GSM8855753 HT29_MYC_AID_IAA_p300
- GSM8855754 HT29_MYC_AID_Ctrl_ETS2
- GSM8855755 HT29_MYC_AID_IAA_ETS2
- GSM8855756 HT29_MYC_AID_Ctrl_BRD4_rep2
- GSM8855757 HT29_MYC_AID_IAA_BRD4_rep2
- GSM8855758 LoVo_MYC_AID_Ctrl_BRD4
- GSM8855759 LoVo_MYC_AID_IAA_BRD4
- GSM8855760 LoVo_MYC_AID_Ctrl_KAT2A
+ 36 more — browse all 76 samples with per-sample file links →
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