德国癌症研究中心Aurelio A. Teleman团队发现，核位置和局部乙酰-CoA的产生调控染色质状态。相关论文于2024年6月5日在线发表在《自然》杂志上。

研究人员揭示了果蝇翅原基上皮组织中组蛋白乙酰化的模式。翅原基外缘的H3K18ac、H4K8ac和总赖氨酸乙酰化都有所增加。这种乙酰化模式受核位置的控制，核在上皮细胞内不断从顶端位置向基底位置移动，在靠近组织表面时表现出高水平的H3K18ac。这些表面细胞核中乙酰-CoA合成酶的含量增加，而乙酰-CoA是组蛋白乙酰化所需的。

组蛋白乙酰化的碳源是脂肪酸的β-氧化作用，这种作用在边缘处也有所增加。抑制脂肪酸β-氧化会导致涉及椎间盘发育的基因的基因组附近的H3K18ac水平下降。总之，果蝇翅膀外缘和其他成虫上皮存在影响基因表达的物理标记。

据悉，组蛋白乙酰化调节基因表达、细胞功能和细胞命运。

附：英文原文

Title: Nuclear position and local acetyl-CoA production regulate chromatin state

Author: Willnow, Philipp, Teleman, Aurelio A.

Issue&Volume: 2024-06-05

Abstract: Histone acetylation regulates gene expression, cell function and cell fate1. Here we study the pattern of histone acetylation in the epithelial tissue of the Drosophila wing disc. H3K18ac, H4K8ac and total lysine acetylation are increased in the outer rim of the disc. This acetylation pattern is controlled by nuclear position, whereby nuclei continuously move from apical to basal locations within the epithelium and exhibit high levels of H3K18ac when they are in proximity to the tissue surface. These surface nuclei have increased levels of acetyl-CoA synthase, which generates the acetyl-CoA for histone acetylation. The carbon source for histone acetylation in the rim is fatty acid β-oxidation, which is also increased in the rim. Inhibition of fatty acid β-oxidation causes H3K18ac levels to decrease in the genomic proximity of genes involved in disc development. In summary, there is a physical mark of the outer rim of the wing and other imaginal epithelia in Drosophila that affects gene expression.

DOI: 10.1038/s41586-024-07471-4

Source: https://www.nature.com/articles/s41586-024-07471-4