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Histone deficiency and hypoacetylation in the aging retinal pigment epithelium.
Dubey, Sushil K; Dubey, Rashmi; Prajapati, Subhash C; Jung, Kyungsik; Mohan, Kabhilan; Liu, Xinan; Roney, Jacob; Tian, Wenjian; Abney, Jennifer; Giarmarco, Michelle M; Hernandez, Alvaro G; Liu, Jinze; Kleinman, Mark E.
Affiliation
  • Dubey SK; Department of Surgery, East Tennessee State University, Johnson City, Tennessee, USA.
  • Dubey R; Department of Surgery, East Tennessee State University, Johnson City, Tennessee, USA.
  • Prajapati SC; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, USA.
  • Jung K; Department of Surgery, East Tennessee State University, Johnson City, Tennessee, USA.
  • Mohan K; Department of Surgery, East Tennessee State University, Johnson City, Tennessee, USA.
  • Liu X; Department of Computer Science, University of Kentucky, Lexington, Kentucky, USA.
  • Roney J; Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, Kentucky, USA.
  • Tian W; Department of Surgery, East Tennessee State University, Johnson City, Tennessee, USA.
  • Abney J; Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, Kentucky, USA.
  • Giarmarco MM; Department of Ophthalmology, University of Washington, Seattle, Washington, USA.
  • Hernandez AG; Roy J. Carver Biotechnology Center, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
  • Liu J; Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia, USA.
  • Kleinman ME; Department of Surgery, East Tennessee State University, Johnson City, Tennessee, USA.
Aging Cell ; 23(5): e14108, 2024 05.
Article in En | MEDLINE | ID: mdl-38408164
ABSTRACT
Histones serve as a major carrier of epigenetic information in the form of post-translational modifications which are vital for controlling gene expression, maintaining cell identity, and ensuring proper cellular function. Loss of histones in the aging genome can drastically impact the epigenetic landscape of the cell leading to altered chromatin structure and changes in gene expression profiles. In this study, we investigated the impact of age-related changes on histone levels and histone acetylation in the retinal pigment epithelium (RPE) and retina of mice. We observed a global reduction of histones H1, H2A, H2B, H3, and H4 in aged RPE/choroid but not in the neural retina. Transcriptomic analyses revealed significant downregulation of histones in aged RPE/choroid including crucial elements of the histone locus body (HLB) complex involved in histone pre-mRNA processing. Knockdown of HINFP, a key HLB component, in human RPE cells induced histone loss, senescence, and the upregulation of senescence-associated secretory phenotype (SASP) markers. Replicative senescence and chronological aging in human RPE cells similarly resulted in progressive histone loss and acquisition of the SASP. Immunostaining of human retina sections revealed histone loss in RPE with age. Acetyl-histone profiling in aged mouse RPE/choroid revealed a specific molecular signature with loss of global acetyl-histone levels, including H3K14ac, H3K56ac, and H4K16ac marks. These findings strongly demonstrate histone loss as a unique feature of RPE aging and provide critical insights into the potential mechanisms linking histone dynamics, cellular senescence, and aging.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Aging / Histones / Retinal Pigment Epithelium Limits: Animals / Humans Language: En Journal: Aging Cell Year: 2024 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Aging / Histones / Retinal Pigment Epithelium Limits: Animals / Humans Language: En Journal: Aging Cell Year: 2024 Document type: Article