Emerson Felicity J, Chiu Caitlin, Lin Laura Y, Riedel Christian G, Zhu Ming, Lee Siu Sylvia
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America.
Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
bioRxiv. 2023 Mar 23:2023.03.20.531974. doi: 10.1101/2023.03.20.531974.
SET-26, HCF-1, and HDA-1 are highly conserved chromatin factors with key roles in development and aging. Here we present mechanistic insights into how these factors regulate gene expression and modulate longevity in . We show that SET-26 and HCF-1 cooperate to regulate a common set of genes, and both antagonize the histone deacetylase HDA-1 to limit longevity. We propose a model in which SET-26 recruits HCF-1 to chromatin in somatic cells, where they stabilize each other at the promoters of a subset of genes, particularly mitochondrial function genes, and regulate their expression. HDA-1 opposes SET-26 and HCF-1 on the regulation of a subset of their common target genes and in longevity. Our findings suggest that SET-26, HCF-1, and HDA-1 comprise a mechanism to fine-tune gene expression and longevity and likely have important implications for the mechanistic understanding of how these factors function in diverse organisms, particularly in aging biology.
SET-26、HCF-1和HDA-1是高度保守的染色质因子，在发育和衰老过程中发挥关键作用。在此，我们阐述了这些因子如何调控基因表达以及调节线虫寿命的机制。我们发现SET-26和HCF-1协同调控一组共同的基因，并且二者均拮抗组蛋白去乙酰化酶HDA-1以限制寿命。我们提出了一个模型，其中SET-26在体细胞中将HCF-1招募至染色质，在那里它们在一部分基因（特别是线粒体功能基因）的启动子处相互稳定，并调节其表达。HDA-1在调控它们共同的一部分靶基因以及寿命方面与SET-26和HCF-1相反。我们的研究结果表明，SET-26、HCF-1和HDA-1构成了一种微调基因表达和寿命的机制，并且可能对理解这些因子在不同生物体中（尤其是衰老生物学中）的作用机制具有重要意义。
