A chromatin perspective on metabolic and genotoxic impacts on hematopoietic stem and progenitor cells.
A chromatin perspective on metabolic and genotoxic impacts on hematopoietic stem and progenitor cells.
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DOI：
10.1007/s00018-020-03522-x
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发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
Jiang H
中科院分区：
文献类型：
--
作者：
Yang Z;Jiang H
造血干细胞和造血祖细胞（hsc和HPCs）自我更新和分化的命运最终是由基因表达决定的，而基因表达又受到全局和局部染色质状态的深刻影响。细胞代谢通过动态调控修饰DNA和组蛋白的酶活性直接影响染色质状态，但也会产生损害DNA的遗传毒性代谢物，从而威胁基因组的完整性。另一方面，调节染色质状态的机制通过调节关键代谢酶的表达和活性来影响代谢。此外，通过直接调节DNA损伤反应或参与该过程的基因表达，染色质调节剂在保护基因组完整性方面发挥着积极而关键的作用，破坏染色质调节剂会导致HSPC功能缺陷。因此，HSPC的功能是由代谢和染色质之间的动态双向相互作用调节的。在这里，我们回顾了从染色质角度研究代谢和遗传毒性因素对HSPC功能和命运决定的主要影响的最新进展。
The fate determination in self-renewal and differentiation of hematopoietic stem and progenitor cells (HSCs and HPCs) is ultimately controlled by gene expression, which is profoundly influenced by the global and local chromatin state. Cellular metabolism directly influences the chromatin state through the dynamic regulation of the enzymatic activities that modify DNA and histones, but also generates genotoxic metabolites that can damage DNA and thus pose threat to the genome integrity. On the other hand, mechanisms modulating the chromatin state impact metabolism by regulating the expression and activities of key metabolic enzymes. Moreover, through regulating either DNA damage response directly or expression of genes involved in this process, chromatin modulators play active and crucial roles in guarding the genome integrity, breaching of which result in defective HSPC function. Therefore, HSPC function is regulated by the dynamic and two-way interactions between metabolism and chromatin. Here, we review recent advances that provide a chromatin perspective on the major impacts the metabolic and genotoxic factors can have on HSPC function and fate determination.
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