Role of ATP-dependent chromatin remodelers in hematopoietic stem and progenitor cell maintenance.
Role of ATP-dependent chromatin remodelers in hematopoietic stem and progenitor cell maintenance.
复制标题
atp依赖性染色质重塑因子在造血干细胞和祖细胞维持中的作用。
DOI：
10.1097/moh.0000000000000710
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发表时间：
2022-07-01
影响因子：
3.2
通讯作者：
Zheng, Yi
中科院分区：
文献类型：
--
作者：
Tu, Zhaowei;Zheng, Yi
关键词：
ATP 依赖性染色质重塑因子利用 ATP 水解产生的能量来调节 DNA 组蛋白结构并调节基因转录。它们在造血过程以及造血干细胞和祖细胞 (HSPC) 功能中至关重要。这篇综述讨论了最近公布的这些染色质重塑剂在 HSPC 调节中的作用，重点是染色质解旋酶 DNA 结合 (CHD) 家族成员的机制。最近对 ATP 依赖性染色质重塑剂的研究表明，个别 CHD 家族成员参与调节 HSPC 细胞命运的不同机制。例如，CHD8 通过限制稳态造血中的 P53 转录活性和蛋白质稳定性来维持 HSPC 的存活，而相关的 CHD7 与 RUNX1 发生物理相互作用，并在血液发育过程中抑制 RUNX1 诱导的 HSPC 扩增。此外，其他 CHD 亚家族成员，如 CHD1/CHD2 和 CHD3/CHD4，以及 SWI/SNF、ISWI 和 INO80 染色质调节剂家族，也被发现通过不同的机制对 HSPC 维持很重要。对造血过程中 ATP 依赖性染色质重塑剂的认识不断丰富，说明了它们各自在 HSPC 维持（包括调节 HSPC 分化、存活和自我更新）中的关键作用。需要进一步的研究来阐明在稳态和应激造血过程中不同的染色质重塑复合物如何整合到各种 HSPC 细胞命运决定中。
ATP-dependent chromatin remodeling factors utilize energy from ATP hydrolysis to modulate DNA-histone structures and regulate gene transcription. They are essential during hematopoiesis and for hematopoietic stem and progenitor cell (HSPC) function. This review discusses the recently unveiled roles of these chromatin remodelers in HSPC regulation, with an emphasis on the mechanism of chromodomain helicase DNA-binding (CHD) family members. Recent studies of ATP-dependent chromatin remodelers have revealed that individual CHD family members engage in distinct mechanisms in regulating HSPC cell fate. For example, CHD8 is required for HSPC survival by restricting both P53 transcriptional activity and protein stability in steady state hematopoiesis while the related CHD7 physically interacts with RUNX1 and suppresses RUNX1-induced expansion of HSPCs during blood development. Moreover, other CHD subfamily members such as CHD1/CHD2 and CHD3/CHD4, as well as the SWI/SNF, ISWI, and INO80 families of chromatin modulators, have also been found important for HSPC maintenance by distinct mechanisms. The expanding knowledge of ATP-dependent chromatin remodelers in hematopoiesis illustrates their respective critical roles in HSPC maintenance including the regulation of HSPC differentiation, survival, and self-renewal. Further studies are warranted to elucidate how different chromatin remodeling complexes are integrated in various HSPC cell fate decisions during steady-state and stress hematopoiesis.