ArticleCellular and molecular gastroenterology and hepatology2020
The Dynamic Chromatin Architecture of the Regenerating Liver.
Article in Cellular and molecular gastroenterology and hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 54 citations in OpenAlex.
- Nucleotide resolution 4-thiouridine sequencing by SNU-Seq and sf4sU-Seq reveals the transcriptional responsiveness of an epigenetically primed human genome.Nucleic acids research · 2026Article
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- Sequential activation of transcription factors promotes liver regeneration through specific and developmental enhancers.Cell genomics · 2025Article
- Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application.Signal transduction and targeted therapy · 2024Review
- Identification of transcription factor co-binding patterns with non-negative matrix factorization.Nucleic acids research · 2024Article
- Review
- Sexually dimorphic renal expression of mouse Klotho is directed by a kidney-specific distal enhancer responsive to HNF1b.Communications biology · 2024Article
- Downregulation of HNF4A enables transcriptomic reprogramming during the hepatic acute-phase response.Communications biology · 2024Article
- Mapping of mitogen and metabolic sensitivity in organoids defines requirements for human hepatocyte growth.Nature communications · 2024Article
- Sexually dimorphic renal expression ofResearch square · 2024Article
- Hepatocyte regeneration is driven by embryo-like DNA methylation reprogramming.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Phosphatidic acid-enabled MKL1 contributes to liver regeneration: Translational implication in liver failure.Acta pharmaceutica Sinica. B · 2024Article
- Post-translational modifications of histone and non-histone proteins in epigenetic regulation and translational applications in alcohol-associated liver disease: Challenges and research opportunities.Pharmacology & therapeutics · 2023Review
- Article
- MDIG-mediated H3K9me3 demethylation upregulates Myc by activating OTX2 and facilitates liver regeneration.Signal transduction and targeted therapy · 2023Article
- Regulation of chromatin organization during animal regeneration.Cell regeneration (London, England) · 2023Review
- Integration of ATAC-Seq and RNA-Seq reveals FOSL2 drives human liver progenitor-like cell aging by regulating inflammatory factors.BMC genomics · 2023Article
- 3D genome perspective on cell fate determination, organ regeneration, and diseases.Cell proliferation · 2023Review
- An autoimmune pleiotropic SNP modulates IRF5 alternative promoter usage through ZBTB3-mediated chromatin looping.Nature communications · 2023Article
- Genetic inhibition of nuclear factor of activated T-cell c2 prevents atrial fibrillation in CREM transgenic mice.Cardiovascular research · 2022Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsThe adult liver is the main detoxification organ and routinely is exposed to environmental insults but retains the ability to restore its mass and function upon tissue damage. However, extensive injury can lead to liver failure, and chronic injury causes fibrosis, cirrhosis, and hepatocellular carcinoma. Currently, the transcriptional regulation of organ repair in the adult liver is incompletely understood.
methodsWe isolated nuclei from quiescent as well as repopulating hepatocytes in a mouse model of hereditary tyrosinemia, which recapitulates the injury and repopulation seen in toxic liver injury in human beings. We then performed the assay for transposase accessible chromatin with high-throughput sequencing specifically in repopulating hepatocytes to identify differentially accessible chromatin regions and nucleosome positioning. In addition, we used motif analysis to predict differential transcription factor occupancy and validated the in silico results with chromatin immunoprecipitation followed by sequencing for hepatocyte nuclear factor 4α (HNF4α) and CCCTC-binding factor (CTCF).
resultsChromatin accessibility in repopulating hepatocytes was increased in the regulatory regions of genes promoting proliferation and decreased in the regulatory regions of genes involved in metabolism. The epigenetic changes at promoters and liver enhancers correspond with the regulation of gene expression, with enhancers of many liver function genes showing a less accessible state during the regenerative process. Moreover, increased CTCF occupancy at promoters and decreased HNF4α binding at enhancers implicate these factors as key drivers of the transcriptomic changes in replicating hepatocytes that enable liver repopulation.
conclusionsOur analysis of hepatocyte-specific epigenomic changes during liver repopulation identified CTCF and HNF4α as key regulators of hepatocyte proliferation and regulation of metabolic programs. Thus, liver repopulation in the setting of toxic injury makes use of both general transcription factors (CTCF) for promoter activation, and reduced binding by a hepatocyte-enriched factor (HNF4α) to temporarily limit enhancer activity. All sequencing data in this study were deposited to the Gene Expression Omnibus database and can be downloaded with accession number GSE109466.
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