The role of DNA methyltransferase 3-like (DNMT3L) gene in megakaryocytic differentiation
| Autor: | Yi-Shan Yu, 俞懿珊 |
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| Rok vydání: | 2017 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 105 Blood cells are produced from hematopoietic stem cells (HSCs) through hematopoiesis to maintain homeostasis. Although various cytokines, signaling molecules and transcription factors are involved in regulation of hematopoiesis, the underlying mechanisms is still not fully understood. DNA methylation, catalyzed by DNA methyltransferases (DNMTs), is an important epigenetic mechanism that regulates numerous physiological and pathological processes. There are five members in DNMT family, including three active enzymes DNMT1, DNMT3A and DNMT3B and one putative RNA methyltransferase DNMT2. The other member that lacks functional methyltransferase domain is DNA methyltransferase 3-like (DNMT3L). Interestingly, DNMT3L can interact with DNMT3A and DNMT3B to modulate their activity and substrate preference. However, the role of DNMT3L in physiological process is almost unclear. Here, we tested whether DNMT3L modulate hematopoiesis. Through knockdown and overexpression approaches, we demonstrated that DNMT3L modulated megakaryocytic differentiation. Most DNMT3L proteins localized in the cytoplasm. Notably, induction of megakaryocytic differentiation did not promote nuclear translocation of DNMT3L, but induced that DNMT3l shuttled to mitochondria. Furthermore, knockdown of DNMT3L affected mitochondria respiration and glycolysis. Taken together, these results demonstrated that DNMT3L translocalized to the mitochondria to regulate mitochondria functions, and then modulate megakaryocytic differentiation. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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