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<p>Histone <span>l</span>-lactylation is a newly identified, metabolism-linked short-chain Lys acylation. Mounting evidence indicates that Lys <span>l</span>-lactylation has key roles in transcription regulation and many other cellular processes and is associated with diverse pathophysiological changes. In this Review, we discuss the&#xa0;unique features of histone <span>l</span>-lactylation, emphasizing the differences between <span>l</span>-lactylation and its isomers, such as <span>d</span>-lactylation. We discuss the regulation of <span>l</span>-lactylation by writers and erasers, its readers and its cofactor <span>l</span>-lactyl-CoA. We highlight the dynamic regulation of nuclear <span>l</span>-lactyl-CoA and <span>l</span>-lactyl-CoA synthetases, which are crucial determinants of the specificity of histone Lys <span>l</span>-lactylation. We also discuss an emerging <span>l</span>-lactyl-CoA-independent <span>l</span>-lactylation pathway. By integrating these findings, we aim to deepen our understanding of the biochemistry and regulation of histone <span>l</span>-lactylation and its broad biological significance.</p>

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Biochemistry and regulation of histone lysine l-lactylation

  • 期刊论文

  • 发表日期：

    2025年8月19日

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  • Xinlei Sheng,
  • Hening Lin,
  • Philip A. Cole,
  • Yingming Zhao

摘要

Histone l-lactylation is a newly identified, metabolism-linked short-chain Lys acylation. Mounting evidence indicates that Lys l-lactylation has key roles in transcription regulation and many other cellular processes and is associated with diverse pathophysiological changes. In this Review, we discuss the unique features of histone l-lactylation, emphasizing the differences between l-lactylation and its isomers, such as d-lactylation. We discuss the regulation of l-lactylation by writers and erasers, its readers and its cofactor l-lactyl-CoA. We highlight the dynamic regulation of nuclear l-lactyl-CoA and l-lactyl-CoA synthetases, which are crucial determinants of the specificity of histone Lys l-lactylation. We also discuss an emerging l-lactyl-CoA-independent l-lactylation pathway. By integrating these findings, we aim to deepen our understanding of the biochemistry and regulation of histone l-lactylation and its broad biological significance.