Histone deacetylase HDA-5 regulates lipid metabolism through H4K5 and H4K8 acetylation in Caenorhabditis elegans

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	Histone deacetylase HDA-5 regulates lipid metabolism through H4K5 and H4K8 acetylation in Caenorhabditis elegans
	Wu, QY; Zhou, M; Zhu, R; Gu, KZ; Ma, YC; Zou, CG
	2025
发表期刊	J. Biol. Chem.
ISSN	0021-9258
卷号	301 期号:12
摘要	Obesity, a widely recognized pathological factor contributing to the onset of metabolic diseases, has been strongly linked to epigenetic modifications. It is ambiguous how his-tone modifications, especially histone acetylation, are involved in lipid metabolism. By analyzing existing transcriptome data of Caenorhabditis elegans glp-1(e2141ts) mutants, we found that the expression of six genes encoding histone deacetylases was significantly up-regulated, which was accompanied by a reduction in the histone H4 acetylation at Lysine 5, 8, 12, and 16 in the germline-deficient worms. Of these histone deacetylases, HDA-4, HDA-5, and SIR-2.2 were involved in reduced histone H4 acetylation modifications in glp-1(e2141ts) mutants. Interestingly, lipid accumulation occurred after knockdown of the three deacetylase genes by RNAi, suggesting that low levels of H4 acetylation are required to maintain lipid homeostasis in glp-1(e2141ts) mutants. In wild-type worms, only knockdown of hda-5 by RNAi led to an increase in both lipid contents and histone modification of H4K5ac and H4K8ac. Integrated analysis of ChIP-seq and RNA-seq data revealed that knockdown of hda-5 by RNAi up-regulated the expression of fatty acid desaturase genes fat-2, fat-4, fat-5, and ttm-5 in H4K5ac and H4K8ac-dependent manners. Upregulation of these genes contributed to lipid accumulation in hda-5 (RNAi) worms. This study elucidates the underlying mechanism by which H4K5ac and H4K8ac modifications regulate lipid homeostasis in C. elegans.
收录类别	SCIE
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/15152
专题	其他
推荐引用方式 GB/T 7714	Wu, QY,Zhou, M,Zhu, R,et al. Histone deacetylase HDA-5 regulates lipid metabolism through H4K5 and H4K8 acetylation in Caenorhabditis elegans[J]. J. Biol. Chem.,2025,301(12).
APA	Wu, QY,Zhou, M,Zhu, R,Gu, KZ,Ma, YC,&Zou, CG.(2025).Histone deacetylase HDA-5 regulates lipid metabolism through H4K5 and H4K8 acetylation in Caenorhabditis elegans.J. Biol. Chem.,301(12).
MLA	Wu, QY,et al."Histone deacetylase HDA-5 regulates lipid metabolism through H4K5 and H4K8 acetylation in Caenorhabditis elegans".J. Biol. Chem. 301.12(2025).

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