HDAC6 deacetylates IDH1 to promote the homeostasis of hematopoietic stem and progenitor cells
HDAC6 deacetylates IDH1 to promote the homeostasis of hematopoietic stem and progenitor cells
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DOI：
10.15252/embr.202256009
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发表时间：
2023-08
期刊：
影响因子：
7.7
通讯作者：
Jia Yang;Yang Liu;Hanxiao Yin;Songbo Xie;Linlin Zhang;Xifeng Dong;Hua Ni;Weiwen Bu;
中科院分区：
文献类型：
--
作者：
Jia Yang;Yang Liu;Hanxiao Yin;Songbo Xie;Linlin Zhang;Xifeng Dong;Hua Ni;Weiwen Bu;
造血干细胞和祖细胞（HSPC）是主要存在于骨髓中并且能够形成成熟血细胞的细胞。然而，支配HSPCs稳态的表观遗传机制仍然难以捉摸。在这里，我们证明了组蛋白去乙酰化酶6（HDAC 6）在调节这一过程中的重要作用。我们的数据显示，由于HSPC增殖减少，Hdac 6敲除小鼠中HSPC的百分比低于野生型小鼠。HDAC 6与异柠檬酸脱氢酶1（IDH 1）相互作用，并在赖氨酸233处使IDH 1脱乙酰。IDH 1的脱乙酰化抑制其催化活性，从而降低10 - 11易位2（TET 2）靶基因的5-羟甲基胞嘧啶水平，改变基因表达模式以促进HSPC的增殖。这些发现揭示了HDAC 6和IDH 1在调节HSPC稳态中的作用，并可能对血液病的治疗产生影响。
Hematopoietic stem and progenitor cells (HSPCs) are cells mainly present in the bone marrow and capable of forming mature blood cells. However, the epigenetic mechanisms governing the homeostasis of HSPCs remain elusive. Here, we demonstrate an important role for histone deacetylase 6 (HDAC6) in regulating this process. Our data show that the percentage of HSPCs in Hdac6 knockout mice is lower than in wild‐type mice due to decreased HSPC proliferation. HDAC6 interacts with isocitrate dehydrogenase 1 (IDH1) and deacetylates IDH1 at lysine 233. The deacetylation of IDH1 inhibits its catalytic activity and thereby decreases the 5‐hydroxymethylcytosine level of ten‐eleven translocation 2 (TET2) target genes, changing gene expression patterns to promote the proliferation of HSPCs. These findings uncover a role for HDAC6 and IDH1 in regulating the homeostasis of HSPCs and may have implications for the treatment of hematological diseases.