过度乙化组合素H4是碳的来源,有助于脂质合成
Evelina Charidemou1, Roberta Noberini2,3, Chiara Ghirardi2,3
1Department of Biological Sciences, University of Cyprus, 2109, Nicosia, Cyprus.
The EMBO journal
|February 22, 2024
概括
基质子储存碳用于脂质合成. 基因素H4的脱乙烯化释放碳,促进脂肪酸的产生,揭示了染色质在新陈代谢中的新作用.
科学领域:
- 细胞的新陈代谢
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 基因突变的修改,如乙化,将环境信号与基因表达联系起来.
- 然而,乙化与转录的相关性是不一致的,这表明在新陈代谢中具有替代作用.
- 染色素在代谢过程中的直接参与仍然在很大程度上未被探索.
研究的目的:
- 为了研究基因组修饰在细胞代谢中的非转录作用.
- 为了确定基质子的修饰是否可以作为代谢物的直接来源.
- 阐明将基因素脱乙烯化与脂质合成联系起来的机制.
主要方法:
- 基于集成质谱的组 histone 修饰映射和代谢学.
- 稳定同位素追踪来追踪碳流.
- 分析肝细胞中的脂质合成,其乙转移酶和脱乙酶活性发生变化.
- 在体内研究使用饮食诱导脂质发生的小鼠模型.
主要成果:
- 乙转移酶枯竭的肝细胞中的脂质升高源于基因素H4的脱乙化.
- 来自海斯顿H4的碳直接促进脂肪酸合成.
- 增强的脂质合成取决于组织素脱乙酶和ACSS2.
- 饮食诱导的脂质发生与体内过度乙化希斯H4水平的降低有关.
- 过度表达乙转移酶可以逆转饮食诱导的脂质生成.
结论:
- 过度乙化组织蛋白作为一种代谢物储存体.
- 歇斯脱乙烯化为脂质合成提供直接的碳来源.
- 这突显了染色体超出基因调节的新奇代谢功能.
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