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核定位和局部乙酰辅酶 A 产生调节染色质状态。

Nuclear position and local acetyl-CoA production regulate chromatin state.

机构信息

German Cancer Research Center (DKFZ), Heidelberg, Germany.

Heidelberg University, Heidelberg, Germany.

出版信息

Nature. 2024 Jun;630(8016):466-474. doi: 10.1038/s41586-024-07471-4. Epub 2024 Jun 5.

DOI:10.1038/s41586-024-07471-4
PMID:38839952
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11168921/
Abstract

Histone acetylation regulates gene expression, cell function and cell fate. 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.

摘要

组蛋白乙酰化调节基因表达、细胞功能和细胞命运。在这里，我们研究了果蝇翅盘上皮组织中组蛋白乙酰化的模式。H3K18ac、H4K8ac 和总赖氨酸乙酰化在外盘缘增加。这种乙酰化模式受核位置控制，核在细胞上皮内从顶端到基底位置连续移动，并在接近组织表面时表现出高水平的 H3K18ac。这些表面核具有较高水平的乙酰辅酶 A 合成酶，它产生用于组蛋白乙酰化的乙酰辅酶 A。边缘中组蛋白乙酰化的碳源是脂肪酸β-氧化，其在边缘也增加。脂肪酸β-氧化的抑制导致参与盘发育的基因附近的 H3K18ac 水平降低。总之，在果蝇中，翅膀和其他成虫上皮的外边缘有一个影响基因表达的物理标记。

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