The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria3052, Australia.
Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
Biochem Soc Trans. 2021 Apr 30;49(2):805-814. doi: 10.1042/BST20200737.
Haematopoiesis is the process by which multipotent haematopoietic stem cells are transformed into each and every type of terminally differentiated blood cell. Epigenetic silencing is critical for this process by regulating the transcription of cell-cycle genes critical for self-renewal and differentiation, as well as restricting alternative fate genes to allow lineage commitment and appropriate differentiation. There are two distinct forms of transcriptionally repressed chromatin: H3K9me3-marked heterochromatin and H3K27me3/H2AK119ub1-marked Polycomb (often referred to as facultative heterochromatin). This review will discuss the role of these distinct epigenetic silencing mechanisms in regulating normal haematopoiesis, how these contribute to age-related haematopoietic dysfunction, and the rationale for therapeutic targeting of these pathways in the treatment of haematological malignancies.
造血是多能造血干细胞转化为各种终末分化血细胞的过程。表观遗传沉默通过调节细胞周期基因的转录对于这个过程至关重要，这些基因对于自我更新和分化至关重要，并且限制了替代命运基因，以允许谱系承诺和适当的分化。有两种截然不同的转录抑制染色质形式：H3K9me3 标记的异染色质和 H3K27me3/H2AK119ub1 标记的 Polycomb（通常称为兼性异染色质）。这篇综述将讨论这些不同的表观遗传沉默机制在调节正常造血中的作用，它们如何导致与年龄相关的造血功能障碍，以及在治疗血液恶性肿瘤时靶向这些途径的治疗合理性。
