ArticleAmerican journal of human genetics2019
Aberrant Function of the C-Terminal Tail of HIST1H1E Accelerates Cellular Senescence and Causes Premature Aging.
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Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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40citing papers in PubMed, 1 pooled it
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Contribution of histone variants to aneuploidy: a cancer perspective.Frontiers in genetics · 2023Pooled it
- Carbon ion irradiation at a clinically used dose rewires super-enhancers to drive necroptosis and systemic immunity.Science advances · 2026Article
- LaminA/C-dependent cellular senescence signaling promotes skeletal muscle atrophy and abnormalities in Parkinson's disease.Cell death & disease · 2026Article
- A Rahman Syndrome mutation in histone H1.4 disrupts chromatin compaction and phase separation.Nature communications · 2026Article
- sc-MULTI-omics approach in nano-rare diseases: understanding the pathophysiological mechanism of Mulvihill-Smith Syndrome.Functional & integrative genomics · 2025Article
- A case of T-cell acute lymphoblastic leukemia in retroviral gene therapy for ADA-SCID.Nature communications · 2024Article
- Development of a mouse embryonic stem cell model for investigating the functions of the linker histone H1-4.FEBS open bio · 2024Article
- A case report of a novel HIST1H1E mutation and a review of the bibliography to evaluate the genotype-phenotype correlations.Molecular genetics & genomic medicine · 2023Review
- Dominantly acting KIF5B variants with pleiotropic cellular consequences cause variable clinical phenotypes.Human molecular genetics · 2023Article
- Post-Translation Modifications and Mutations of Human Linker Histone Subtypes: Their Manifestation in Disease.International journal of molecular sciences · 2023Review
- Histone variants and chromatin structure, update of advances.Computational and structural biotechnology journal · 2023Review
- Pan-Cancer Analysis of the Tumorigenic Effect and Prognostic Diagnostic Value of FAM111B in Human Carcinomas.International journal of general medicine · 2023Article
- Epigenetic regulation of aging: implications for interventions of aging and diseases.Signal transduction and targeted therapy · 2022Review
- Structural Mechanism of TAF-Iβ Chaperone Function on Linker Histone H1.10.Journal of molecular biology · 2022Article
- Analysis of histone variant constraint and tissue expression suggests five potential novel human disease genes: H2AFY2, H2AFZ, H2AFY, H2AFV, H1F0.Human genetics · 2022Article
- Article
- Mutations of the histone linker H1-4 in neurodevelopmental disorders and functional characterization of neurons expressing C-terminus frameshift mutant H1.4.Human molecular genetics · 2022Article
- Recurrent de novo missense variants across multiple histone H4 genes underlie a neurodevelopmental syndrome.American journal of human genetics · 2022Article
- Expanding the mutational spectrum of Rahman syndrome: A rare disorder with severe intellectual disability and particular facial features in two Chinese patients.Molecular genetics & genomic medicine · 2022Article
- Exome sequencing identified a novel HIST1H1E heterozygous protein-truncating variant in a 6-month-old male patient with Rahman syndrome: A case report.Clinical case reports · 2022Article
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Authors and funding
60 authors at 20 institutions in 8 countries.
Elisabetta FlexDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, 00161 Italy; Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY 10467, USA.
Simone MartinelliDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, 00161 Italy.
Anke Van DijckDepartment of Medical Genetics, University of Antwerp, Edegem, 2650 Belgium; Department of Neurology, Antwerp University Hospital, Edegem, 2650 Belgium.
Andrea CiolfiGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, 00146 Italy.
Serena CecchettiMicroscopy Area, Core Facilities, Istituto Superiore di Sanità, Rome, 00161 Italy.
Elisa ColuzziDepartment of Science, University Roma Tre, Rome, 00146 Italy.
Luca PannoneDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, 00161 Italy; Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, 00146 Italy.
Cristina AndreoliDepartment of Environment and Health, Istituto Superiore di Sanità, Rome, 00161 Italy.
Francesca Clementina RadioGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, 00146 Italy.
Simone PizziGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, 00146 Italy.
Giovanna CarpentieriDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, 00161 Italy; Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, 00146 Italy.
Alessandro BrusellesDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, 00161 Italy.
Giuseppina CatanzaroDepartment of Experimental Medicine, Sapienza University, Rome, 00161 Italy.
Lucia PedaceDepartment of Pediatric Onco-Hematology and Cell and Gene Therapy, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, 00146 Italy.
Evelina MieleDepartment of Pediatric Onco-Hematology and Cell and Gene Therapy, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, 00146 Italy.
Elena CarcarinoDepartment of Pediatric Onco-Hematology and Cell and Gene Therapy, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, 00146 Italy; Current affiliation: Cordeliers Research Centre, Inserm 1138, Sorbonne Université, Paris, 75006 France.
Xiaoyan GeDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Current affiliation: Department of Genetics and Genomic Sciences, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Chieko ChijiwaDepartment of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6H 3N1, Canada.
M E Suzanne LewisDepartment of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6H 3N1, Canada.
Marije MeuwissenDepartment of Medical Genetics, University of Antwerp, Edegem, 2650 Belgium.
Sandra KenisDepartment of Neurology, Antwerp University Hospital, Edegem, 2650 Belgium.
Nathalie Van der AaDepartment of Medical Genetics, University of Antwerp, Edegem, 2650 Belgium.
Austin LarsonSection of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Kathleen BrownSection of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Melissa P WassersteinChildren's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY 10467, USA.
Brian G SkotkoDivision of Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02114, USA.
Amber BegtrupGeneDx, Gaithersburg, MD 20877, USA.
Richard PersonGeneDx, Gaithersburg, MD 20877, USA.
Maria KarayiorgouDepartment of Psychiatry, Columbia University Medical Center, New York, NY 10032, USA.
J Louw RoosDepartment of Psychiatry, University of Pretoria, Weskoppies Hospital, Pretoria, 0001 South Africa.
Koen L Van GassenDepartment of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, 3508 AB the Netherlands.
Marije KoopmansDepartment of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, 3508 AB the Netherlands.
Emilia K BijlsmaDepartment of Clinical Genetics, Leiden University Medical Center, Leiden, 2300 RC the Netherlands.
Gijs W E SantenDepartment of Clinical Genetics, Leiden University Medical Center, Leiden, 2300 RC the Netherlands.
Daniela Q C M Barge-SchaapveldDepartment of Clinical Genetics, Leiden University Medical Center, Leiden, 2300 RC the Netherlands.
Claudia A L RuivenkampDepartment of Clinical Genetics, Leiden University Medical Center, Leiden, 2300 RC the Netherlands.
Mariette J V HofferDepartment of Clinical Genetics, Leiden University Medical Center, Leiden, 2300 RC the Netherlands.
Seema R LalaniDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Haley StreffDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
William J CraigenDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Brett H GrahamDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Annette P M van den ElzenDepartement of Pediatrics, Reinier de Graaf Ziekenhuis, Delft, 2600 GA the Netherlands.
Daan J KamphuisDepartement of Neurology, Reinier de Graaf Ziekenhuis, Delft, 2600 GA the Netherlands.
Katrin ÕunapDepartment of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu, 50406 Estonia; Institute of Clinical Medicine, University of Tartu, Tartu, 50406 Estonia.
Karit ReinsonDepartment of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu, 50406 Estonia; Institute of Clinical Medicine, University of Tartu, Tartu, 50406 Estonia.
Sander PajusaluDepartment of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu, 50406 Estonia; Institute of Clinical Medicine, University of Tartu, Tartu, 50406 Estonia; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Monica H WojcikBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Clara VibertiDepartment of Medical Sciences, University of Turin, Turin, 10126 Italy; Italian Institute for Genomic Medicine, Turin, 10126 Italy.
Cornelia Di GaetanoDepartment of Medical Sciences, University of Turin, Turin, 10126 Italy; Italian Institute for Genomic Medicine, Turin, 10126 Italy.
Enrico BertiniGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, 00146 Italy.
Simona PetrucciDepartment of Clinical and Molecular Medicine, Sapienza University, Rome, 00189 Italy; Division of Medical Genetics, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, 71013 Italy.
Alessandro De LucaDivision of Medical Genetics, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, 71013 Italy.
Rossella RotaDepartment of Pediatric Onco-Hematology and Cell and Gene Therapy, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, 00146 Italy.
Elisabetta FerrettiDepartment of Experimental Medicine, Sapienza University, Rome, 00161 Italy; Istituto Neuromed, IRCCS, Pozzilli, 86077 Italy.
Giuseppe MatulloDepartment of Medical Sciences, University of Turin, Turin, 10126 Italy; Italian Institute for Genomic Medicine, Turin, 10126 Italy.
Bruno DallapiccolaGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, 00146 Italy.
Antonella SguraDepartment of Science, University Roma Tre, Rome, 00146 Italy.
Magdalena WalkiewiczDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Current affiliation: National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA.
R Frank KooyDepartment of Medical Genetics, University of Antwerp, Edegem, 2650 Belgium. Electronic address: frank.kooy@uantwerpen.be.
Marco TartagliaGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, 00146 Italy. Electronic address: marco.tartaglia@opbg.net.
Bambino Gesù Children's Hospital · ITBaylor College of Medicine · USLeiden University Medical Center · NLIstituti di Ricovero e Cura a Carattere Scientifico · ITIstituto Superiore di Sanità · ITUniversity of Antwerp · BEAntwerp University Hospital · BEItalian institute for Genomic Medicine · ITReinier de Graaf Hospital · NLRoma Tre University · ITSapienza University of Rome · ITTartu University Hospital · EEUniversity of British Columbia · CAUniversity of Colorado Denver · USUtrecht University · NLAlbert Einstein College of Medicine · USBroad Institute · USCasa Sollievo della Sofferenza · ITChildren's Hospital at Montefiore · USColumbia University Irving Medical Center · US
Funding
Joint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5MTRAINING GRANT IN GENETICST32GM007748 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Anne O'Donnell-Luria, Louise Wilkins-Haug · 1985 to 2026
$12.0MNHGRI NIH HHS UM1 HG008900NIGMS NIH HHS T32 GM007748
Abstract
Histones mediate dynamic packaging of nuclear DNA in chromatin, a process that is precisely controlled to guarantee efficient compaction of the genome and proper chromosomal segregation during cell division and to accomplish DNA replication, transcription, and repair. Due to the important structural and regulatory roles played by histones, it is not surprising that histone functional dysregulation or aberrant levels of histones can have severe consequences for multiple cellular processes and ultimately might affect development or contribute to cell transformation. Recently, germline frameshift mutations involving the C-terminal tail of HIST1H1E, which is a widely expressed member of the linker histone family and facilitates higher-order chromatin folding, have been causally linked to an as-yet poorly defined syndrome that includes intellectual disability. We report that these mutations result in stable proteins that reside in the nucleus, bind to chromatin, disrupt proper compaction of DNA, and are associated with a specific methylation pattern. Cells expressing these mutant proteins have a dramatically reduced proliferation rate and competence, hardly enter into the S phase, and undergo accelerated senescence. Remarkably, clinical assessment of a relatively large cohort of subjects sharing these mutations revealed a premature aging phenotype as a previously unrecognized feature of the disorder. Our findings identify a direct link between aberrant chromatin remodeling, cellular senescence, and accelerated aging.
Indexed as
AneuploidyCell NucleolusCellular SenescenceChildChromatinDNA MethylationFemaleHistonesHumansInfantMaleMiddle AgedChromatinHistonesaccelerated agingcellular senescencechromatin compactionchromatin dynamicschromatin remodelingHIST1H1Elinker histonelinker histone H1.4methylation profilingreplicative senescence
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