ArticleNature genetics2022
Histone H3 proline 16 hydroxylation regulates mammalian gene expression.
Erratum issuedOpen access · greenAbstract read
In one paragraph
Article in Nature genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.
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26citing papers in PubMed
3.7field-weighted citation impact, top 5% of its field
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Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- PHD1-dependent hydroxylation of RepoMan (CDCA2) on P604 modulates the control of mitotic progression.eLife · 2026Article
- Obesity Disrupts H3K4me3-Mediated Lactate Accumulation and Efferocytosis in Hypoxic Macrophages.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- FBXO39 knockdown promotes spermatogenesis impairment by inducing mitochondrial dysfunction and ferroptosis via inhibiting KDM5A ubiquitination and regulating H3K4me3 demethylation.Cell biology and toxicology · 2026Article
- Stage-Specific Regulation of Ubiquitination Modifications and Prospects for Targeted Therapy in Triple-Negative Breast Cancer.Oncology research · 2026Review
- Mapping Non-Coding Epimutations in Breast Cancer: Advancing Epigenetics Towards Precision Medicine.Sub-cellular biochemistry · 2026Review
- Histone lysine demethylases in breast cancer: molecular mechanisms, biological functions, and therapeutic intervention.Molecular cancer · 2025Review
- Transferrin promotes fatty acid oxidation and liver tumor growth through PHD2-mediated PPARα hydroxylation in an iron-dependent manner.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Elucidating the Pharmacological Basis of Xianling Cifang Granules Against Breast Cancer. A Metabolomic Profiling Study.Drug design, development and therapy · 2025Article
- Global maintenance of histone post-translational modifications during the transition into anoxia in embryos of the annual killifishEnvironmental epigenetics · 2025Article
- Deubiquitinating enzyme mutagenesis screens identify a USP43-dependent HIF-1 transcriptional response.The EMBO journal · 2024Article
- Exploring histone deacetylases in type 2 diabetes mellitus: pathophysiological insights and therapeutic avenues.Clinical epigenetics · 2024Review
- KDM5 family as therapeutic targets in breast cancer: Pathogenesis and therapeutic opportunities and challenges.Molecular cancer · 2024Review
- Von Hippel Lindau tumor suppressor controls m6A-dependent gene expression in renal tumorigenesis.The Journal of clinical investigation · 2024Article
- Transcriptional elongation control of hypoxic response.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Development of Complementary Photo-arginine/lysine to Promote Discovery of Arg/Lys hPTMs Interactomes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The P124A mutation of SRP14 alters its migration on SDS-PAGE without impacting its function.Acta biochimica et biophysica Sinica · 2024Article
- Hypoxia-inducible factor in cancer: from pathway regulation to therapeutic opportunity.BMJ oncology · 2024Review
- Oxygen-regulated post-translation modifications as master signalling pathway in cells.EMBO reports · 2023Review
- Recent developments in catalysis and inhibition of the Jumonji histone demethylases.Current opinion in structural biology · 2023Review
- A mitochondrial EglN1-AMPKα axis drives breast cancer progression by enhancing metabolic adaptation to hypoxic stress.The EMBO journal · 2023Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
27 authors at 5 institutions in 2 countries.
Xijuan Liu *Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jun Wang *Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Joshua A BoyerLineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-3990-4096
Weida GongLineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-0046-9277
Shuai ZhaoLineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Ling XieDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Qiong WuDepartment of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Cheng ZhangDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Kanishk JainLineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Yiran GuoLineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-6266-9186
Javier RodriguezCancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Mingjie LiDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Hidetaka UryuLineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Chengheng LiaoDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-9073-3835
Lianxin HuDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0001-5600-5634
Jin ZhouDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Xiaobing ShiCenter for Epigenetics, Van Andel Institute, Grand Rapids, MI, USA.ORCID http://orcid.org/0000-0001-5242-8189
Yi-Hsuan TsaiLineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-2107-4300
Qin YanDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-4077-453X
Weibo LuoDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Xian ChenDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Brian D StrahlLineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-4947-6259
Alex von KriegsheimCancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Qi ZhangLineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-1754-4058
Gang Greg WangLineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-7210-9940
Albert S BaldwinLineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Qing ZhangDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA. Qing.Zhang@UTSouthwestern.edu.ORCID http://orcid.org/0000-0002-6595-8995
University of North Carolina at Chapel Hill · USThe University of Texas Southwestern Medical Center · USEdinburgh Cancer Research · GBVan Andel Institute · USYale University · US
Funding
Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI David Darr · 1985 to 2026
$201.5MYale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MIKK/NF-kappaB Signaling in Cancer: Therapy, Resistance, and Tumor Initiating CellsR35CA197684 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BALDWIN, ALBERT SIDNEY · 2016 to 2022
$5.8MMechanisms of chromatin and transcriptional regulationR35GM126900 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Brian D Strahl · 2018 to 2026
$5.5MExploration of ZHX2 as a novel substrate of pVHL and an oncogenic driver of renal cancerR01CA211732 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI ZHANG, QING · 2017 to 2021
$2.1MBBOX1 is a Novel Oncogenic Driver in Triple Negative Breast CancerR01CA256833 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI ZHANG, QING · 2021 to 2025
$2.0MCancer Epigenetics: A novel PRC2 Dysregulation Mechanism in Multiple MyelomaR01CA211336 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WANG, G GREG · 2017 to 2021
$2.0MDetermining the Role of DNA Methylation Deregulation in OncogenesisR01CA215284 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WANG, G GREG · 2017 to 2021
$1.7MNCATS NIH HHS UL1 TR001863NCI NIH HHS P30 CA016086NCI NIH HHS R01 CA211336NCI NIH HHS R01 CA211732NCI NIH HHS R01 CA215284NCI NIH HHS R01 CA256833NCI NIH HHS R35 CA197684NIGMS NIH HHS R35 GM126900
Abstract
Histone post-translational modifications (PTMs) are important for regulating various DNA-templated processes. Here, we report the existence of a histone PTM in mammalian cells, namely histone H3 with hydroxylation of proline at residue 16 (H3P16oh), which is catalyzed by the proline hydroxylase EGLN2. We show that H3P16oh enhances direct binding of KDM5A to its substrate, histone H3 with trimethylation at the fourth lysine residue (H3K4me3), resulting in enhanced chromatin recruitment of KDM5A and a corresponding decrease of H3K4me3 at target genes. Genome- and transcriptome-wide analyses show that the EGLN2-KDM5A axis regulates target gene expression in mammalian cells. Specifically, our data demonstrate repression of the WNT pathway negative regulator DKK1 through the EGLN2-H3P16oh-KDM5A pathway to promote WNT/β-catenin signaling in triple-negative breast cancer (TNBC). This study characterizes a regulatory mark in the histone code and reveals a role for H3P16oh in regulating mammalian gene expression.
Indexed as
HistonesProlineAnimalsGene ExpressionHydroxylationMammalsMethylationHistonesProline
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