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Chapitre D'ouvrage Année : 2024

Epigenetically decipherING the genome: A role for PHDs

Résumé

While completion of the initial phase of the human genome project redefined genetics over two decades ago, the field of epigenetics is currently redefining how chromatin structure affects the gene expression to mold the proteome and the cell phenotype. Posttranslational modification (PTM) of nucleic acids and proteins is central to chromatin organization and helps govern transcription and translation to affect specific phenotypes. Zinc fingers are a common constituent of chromatin regulators and the plant homeodomain (PHD) forms of zinc finger function as readers of the histone code. Understanding the structural mechanisms driving the recognition of PTMs by PHDs is at the core of efforts to understand how chromatin architecture is maintained and modulated. Here, we describe the roles of PHD finger proteins in chromatin remodeling through their specific binding to PTMs on histone proteins with an emphasis on the Inhibitor of Growth (ING) family. Once bound to methylated chromatin, ING1-5 family members serve as scaffolds for the docking of complexes of effector proteins that are vital to gene-specific activation and/or inactivation events that occur within chromatin. All members of the ING family recognize different methylated forms of lysine 4 near the amino terminus of core histone 3 (H3K4me1/2/3), but different members target either histone acetyltransferase (HAT) or histone deacetylase (HDAC) complexes to regulate histone acetylation and subsequently chromatin structure and gene expression. ING-mediated changes in gene expression have now been shown to profoundly affect a broad range of biological processes including development, differentiation, cellular senescence, and oncogenesis. © 2024 Elsevier Inc. All rights reserved.
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Dates et versions

hal-04337506 , version 1 (12-12-2023)

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Gesche Riabowol Née Tallen, Yang Yang, Arthur Dantas, Daniel Udenwobele, Arash Nabbi, et al.. Epigenetically decipherING the genome: A role for PHDs. Chromatin Readers in Health and Disease, 35, Elsevier, pp.217-238, 2024, 978-012823376-4; 978-032390314-1. ⟨10.1016/B978-0-12-823376-4.00003-3⟩. ⟨hal-04337506⟩
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