Evidence map›Paper›PMID 38909044›Full record

ArticleNature communications2024

HNF4A and HNF1A exhibit tissue specific target gene regulation in pancreatic beta cells and hepatocytes.

Natasha Hui Jin Ng, Soumita Ghosh, Chek Mei Bok, Carmen Ching, Blaise Su Jun Low, Juin Ting Chen, Euodia Lim, María Clara Miserendino, Yaw Sing Tan, Shawn Hoon and 1 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
–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

35 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  20. Frontiers in endocrinology · 2026
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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

11 authors.

Natasha Hui Jin NgStem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, 138673, Singapore.ORCID http://orcid.org/0000-0002-1094-4967
Soumita GhoshDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore.
Chek Mei BokStem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, 138673, Singapore.
Carmen ChingStem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, 138673, Singapore.
Blaise Su Jun LowStem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, 138673, Singapore.ORCID http://orcid.org/0000-0003-3304-0861
Juin Ting ChenStem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, 138673, Singapore.
Euodia LimStem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, 138673, Singapore.
María Clara MiserendinoFacultad de Ciencias Químicas, Universidad Nacional de Córdoba, X5000HUA, Córdoba, Argentina.
Yaw Sing TanBioinformatics Institute, A*STAR, Singapore, 138671, Singapore.ORCID http://orcid.org/0000-0002-2522-9421
Shawn HoonMolecular Engineering Laboratory, IMCB, A*STAR, Singapore, 138673, Singapore.
Adrian Kee Keong TeoStem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, 138673, Singapore. ateo@imcb.a-star.edu.sg.ORCID http://orcid.org/0000-0001-5901-7075

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

HNF4A and HNF1A encode transcription factors that are important for the development and function of the pancreas and liver. Mutations in both genes have been directly linked to Maturity Onset Diabetes of the Young (MODY) and type 2 diabetes (T2D) risk. To better define the pleiotropic gene regulatory roles of HNF4A and HNF1A, we generated a comprehensive genome-wide map of their binding targets in pancreatic and hepatic cells using ChIP-Seq. HNF4A was found to bind and regulate known (ACY3, HAAO, HNF1A, MAP3K11) and previously unidentified (ABCD3, CDKN2AIP, USH1C, VIL1) loci in a tissue-dependent manner. Functional follow-up highlighted a potential role for HAAO and USH1C as regulators of beta cell function. Unlike the loss-of-function HNF4A/MODY1 variant I271fs, the T2D-associated HNF4A variant (rs1800961) was found to activate AKAP1, GAD2 and HOPX gene expression, potentially due to changes in DNA-binding affinity. We also found HNF1A to bind to and regulate GPR39 expression in beta cells. Overall, our studies provide a rich resource for uncovering downstream molecular targets of HNF4A and HNF1A that may contribute to beta cell or hepatic cell (dys)function, and set up a framework for gene discovery and functional validation.

Indexed as

Diabetes Mellitus, Type 2Gene Expression RegulationHepatocyte Nuclear Factor 1-alphaHepatocyte Nuclear Factor 4HepatocytesInsulin-Secreting CellsA Kinase Anchor ProteinsAnimalsHumansMiceOrgan SpecificityA Kinase Anchor ProteinsHepatocyte Nuclear Factor 1-alphaHepatocyte Nuclear Factor 4HNF1A protein, humanHNF4A protein, human

Identifiers

PMID38909044
PMCPMC11193738

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.