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<p>Histone post-translational modifications epigenetically regulate gene expression by modulating nucleosome structure and DNA accessibility. This review outlines how&#xa0;unique patterns of modifications on canonical and variant histones&#xa0;generate a combinatorial histone code. Interplay between multiple modifications increases the complexity as distinct histone proteoforms and nucleoforms can drive context-dependent outcomes. The histone code is highly dynamic, and we examine how histone modifications fluctuate with environmental cues, metabolic state, and cell-cycle progression. Finally, we discuss how dysregulation of histone modifications contributes to disease, and how emerging technologies to decipher the histone code are yielding new biological insights and opportunities for therapeutic development.</p>

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Unraveling the complexity of the histone code: implications for gene regulation and disease

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月24日

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  • Kiera L. Malone,
  • Ajit K. Singh,
  • James M. Lignos,
  • Elizabeth D. Cook,
  • Margaret Phillips,
  • Brian W. Boyle,
  • Isabelle A. Kressy,
  • Mirabella Vulikh,
  • Annika K. Lathrop,
  • Kyle T. McKay,
  • Hassan Zafar,
  • Janet L. Stein,
  • Gary S. Stein,
  • Karen C. Glass

摘要

Histone post-translational modifications epigenetically regulate gene expression by modulating nucleosome structure and DNA accessibility. This review outlines how unique patterns of modifications on canonical and variant histones generate a combinatorial histone code. Interplay between multiple modifications increases the complexity as distinct histone proteoforms and nucleoforms can drive context-dependent outcomes. The histone code is highly dynamic, and we examine how histone modifications fluctuate with environmental cues, metabolic state, and cell-cycle progression. Finally, we discuss how dysregulation of histone modifications contributes to disease, and how emerging technologies to decipher the histone code are yielding new biological insights and opportunities for therapeutic development.