Histone lysine succinylation: a comprehensive review of enzymatic pathways and disease associations

Abstract

Histone post-translational modifications (HPTMs) are essential for chromatin structure, transcriptional regulation, and DNA repair. Lysine succinylation (Ksuc), a recently identified HPTM, involves the addition of succinyl groups to lysine residues, altering their chemical environment and impacting histone-DNA interactions. This review provides a detailed account of histone lysine succinylation, focusing on its research history, specific modification sites, and regulatory mechanisms. Succinylation primarily occurs at the globular domain and C-terminal regions of histones, with key sites such as H3K79 and H3K122 extensively being studied. Succinyl-CoA serves as the donor molecule for this modification, with enzymatic pathways involving KAT2A, HAT1, and p300, as well as non-enzymatic pathways influenced by metabolic intermediates. Desuccinylation is regulated by enzymes such as sirtuin family and HDAC family members. Histone lysine succinylation enhances chromatin accessibility, promotes gene transcription, and facilitates DNA damage repair. Additionally, this modification is implicated in the progression of diseases such as cancer and hepatitis B virus (HBV) infection, highlighting its potential as a therapeutic target. By exploring the interplay between histone succinylation and cellular metabolism, this review underscores the significance of this novel modification in epigenetic regulation and disease development.

Lead Contact: Jinke Gu.

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Keywords

Histone / Succinylation / Desuccinylation / Chromatin dynamics / Disease

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Funding

National Natural Science Foundation of China(32270832)

Basic and Applied Basic Research Foundation of Guangdong Province(2023B1515020039)

Shenzhen Science and Technology Innovation Program(RCYX20221008092904016)

Shenzhen University 2035 Program for Excellent Research(2022C012)

RIGHTS & PERMISSIONS

Shenzhen University School of Medicine; Fondazione Istituto FIRC di Oncologia Molecolare