Evidence map›Paper›PMID 42345195›Full record

ArticleNucleic acids research2026

Dynamics and master transcription factors dependence of intestinal super-enhancers during differentiation and oncogenesis.

Wenxin Fang, Shuya Huang, Ruoxuan Xiao, Guangling Wei, Mingyang Zhang, Xia Qiu, Li Zou, Michael P Verzi, Yan Wang, Lei Chen

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nucleic acids research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Wenxin FangJiangsu Provincial Key Laboratory of Critical Care Medicine, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing 210031, China.
Shuya HuangJiangsu Provincial Key Laboratory of Critical Care Medicine, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing 210031, China.
Ruoxuan XiaoJiangsu Provincial Key Laboratory of Critical Care Medicine, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing 210031, China.
Guangling WeiJiangsu Provincial Key Laboratory of Critical Care Medicine, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing 210031, China.
Mingyang ZhangJiangsu Provincial Key Laboratory of Critical Care Medicine, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing 210031, China.
Xia QiuDepartment of Genetics, Rutgers University, Piscataway, NJ 08854, United States.
Li ZouJiangsu Provincial Key Laboratory of Critical Care Medicine, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing 210031, China.
Michael P VerziDepartment of Genetics, Rutgers University, Piscataway, NJ 08854, United States.
Yan WangCenter for Translational Medicine Research and Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.ORCID 0000-0003-0671-7312
Lei ChenJiangsu Provincial Key Laboratory of Critical Care Medicine, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing 210031, China.ORCID 0000-0001-7812-508X

Funding

Fundamental Research Funds for the Central Universities 2242025F10003National Key R&D Program of China 2023YFA1801500National Natural Science Foundation of China 32270830National Natural Science Foundation of China U25A2016Nature Science Foundation of Jiangsu Province BK20230026NIH HHSSoutheast University Interdisciplinary Research Program for Young Scholars 2024FGC1003University's Start-up Research Fund R01DK126446University's Start-up Research Fund RF1028623015
6 · The paper itself

Abstract

The intestinal epithelium is a highly regenerative tissue organized along the crypt-villus axis, where spatially compartmentalized gene expression governs stem cell renewal, proliferation, and differentiation. Super-enhancers (SEs) are large clusters of regulatory elements densely bound by transcription factors (TFs) and cofactors that drive high-level expression of genes controlling cell identity and fate, yet their roles in intestinal epithelial identity and differentiation remain unclear. Here, we generate a spatiotemporal map of SEs in the small intestine, identifying compartment-specific SEs that define crypt and villus programs. Using mouse genetic models, we identify CDX2, HNF4, and SMAD4 as core TFs orchestrating SE-driven transcriptional networks essential for epithelial differentiation. CDX2 is required for SE integrity, and its loss causes widespread SE collapse and silencing of intestinal identity genes. We further demonstrate SE remodeling during colorectal cancer, in which HNF4 and SMAD4 function as SE-associated tumor suppressors that restrain oncogenic enhancer programs. Together, our findings establish SEs as central regulators of intestinal architecture, epithelial fidelity, and tumor progression.

Indexed as

CarcinogenesisCell DifferentiationIntestinal MucosaSuper EnhancersTranscription FactorsAnimalsCDX2 Transcription FactorGene Regulatory NetworksHepatocyte Nuclear Factor 4Intestine, SmallMiceSmad4 ProteinCdx2 protein, mouseCDX2 Transcription FactorHepatocyte Nuclear Factor 4Hnf4a protein, mouseSmad4 ProteinSmad4 protein, mouseTranscription Factors

Identifiers

PMID42345195
PMCPMC13294677

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.