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Hepatocyte nuclear factor 4-alpha (HNF4α) is a master regulator gene belonging to the nuclear receptor superfamily and is involved in regulating a wide range of critical biological processes in different organs. Structurally, the HNF4A locus is organized into two independent promoters and is subjected to alternative splicing to produce twelve distinct isoforms. However, little is known about the biological impact of each isoform and the mechanisms by which they regulate transcription. Proteomic analyses have led to the identification of proteins that interact with specific HNF4α isoforms. The identification and validation of these interactions and their roles in the co-regulation of targeted gene expression are essential to better understand the role of this transcription factor in different biological processes and pathologies. This review addresses the discoveries of different HNF4α isoforms and the main functions of the P1 and P2 isoform subgroups. It also provides information on the most recent focus areas in research on the nature and function of proteins associated with each of the isoforms in some biological contexts.
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http://dx.doi.org/10.1002/pmic.202200372 | DOI Listing |
Nat Commun
September 2025
Department of Biochemistry, University of Illinois, Urbana-Champaign, IL, USA.
Individuals with progressive liver failure risk dying without liver transplantation. However, our understanding of why regenerative responses are disrupted in failing livers is limited. Here, we perform multiomic profiling of healthy and diseased human livers using bulk and single-nucleus RNA- and ATAC-seq.
View Article and Find Full Text PDFBiochem Pharmacol
September 2025
Pharmacy College of Shihezi University/Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education/Institute for Safflower Industry Research of Shihezi University, Shihezi University, North 4th Road 221, Shihezi, China. Electronic address:
The etiology of alcoholic fatty liver (AFL) is complex, representing the early reversible stage of alcohol-associated liver disease (ALD). Alleviating oxidative stress, reducing inflammation, and preventing the development of liver fibrosis are considered the most effective strategies for treating AFL. Consequently, we selected isoliquiritigenin (ISL), a flavonoid compound recognized for its anti-inflammatory, antioxidant, and anticancer pharmacological properties.
View Article and Find Full Text PDFPLoS Pathog
September 2025
State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
Hepatocyte nuclear factor 4 alpha (Hnf4α), a conserved nuclear receptor central to vertebrate liver development and metabolic regulation, emerges here as a pivotal immune regulator in teleosts against complex infectious threats. While its metabolic roles are well-established, Hnf4α's function in bacterial infection, viral infection, and bacterial-viral coinfection-major challenges in global aquaculture-remained uncharacterized. This study reveals that teleost Hnf4α acts as a dual-functional immune checkpoint, essential for combating Aeromonas salmonicida, grass carp reovirus (GCRV), and their coinfection.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
September 2025
Institute of Pharmacology and Toxicology, Goethe University Frankfurt, Frankfurt, Germany.
The A20 binding inhibitor of nuclear factor-kappa B (NF-κB)-1 (ABIN-1) serves as a ubiquitin sensor and autophagy receptor, crucial for modulating inflammation and cell death. Our previous in vitro investigation identified the LC3-interacting region (LIR) motifs 1 and 2 of ABIN-1 as key mitophagy regulators. This study aimed to explore the in vivo biological significance of ABIN1-LIR domains using a novel CRISPR-engineered ABIN1-ΔLIR1/2 mouse model, which lacks both LIR motifs.
View Article and Find Full Text PDFAdv Sci (Weinh)
September 2025
China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Immune Response and Immunotherapy, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, GIBH-CUHK Joint Resea
TP53 mutations are highly associated with hepatocellular carcinoma (HCC), a common and deadly cancer. However, few primary drivers in the progression of HCC with mutant TP53 have been identified. To uncover tumor suppressors in human HCC, a genome-wide CRISPR/Cas9-based screening of primary human hepatocytes with MYC and TP53 overexpression (MT-PHHs) is performed in xenografts.
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