A regulatory circuit comprising GATA1/2 switch and microRNA-27a/24 promotes erythropoiesis.
A regulatory circuit comprising GATA1/2 switch and microRNA-27a/24 promotes erythropoiesis.
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由 GATA1/2 开关和 microRNA-27a/24 组成的调节电路促进红细胞生成
DOI：
10.1093/nar/gkt848
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发表时间：
2014-01
影响因子：
14.9
通讯作者：
Yu J
中科院分区：
文献类型：
--
作者：
Wang F;Zhu Y;Guo L;Dong L;Liu H;Yin H;Zhang Z;Li Y;Liu C;Ma Y;Song W;He A;Wang Q;Wang L;Zhang J;Li J;Yu J
转录网络协调复杂的发育过程，这种网络通常由发育的主调节器煽动。到目前为止，在阐明控制红细胞发育的加塔因子依赖性遗传网络方面已经取得了相当大的进展。在此，我们报道了加塔-1和加塔-2共调节两个microRNA基因microRNA-27 a和microRNA-24的表达，这两个基因在调节红系分化中具有关键作用。一般来说，加塔-2占据了miR-27 α 24启动子并抑制其在未成熟红系祖细胞中的转录。随着红细胞生成的进行，加塔-1直接激活miR-27 a转录，这涉及加塔-1介导的加塔-2从染色质的置换，这一过程称为“加塔开关”。此外，成熟的miR-27 a和miR-24协同抑制加塔-2的翻译，并促进从加塔-2到加塔-1的占据转换，从而完成促进红系成熟的正反馈回路。与加塔因子的基本作用一致，miR-27 a或miR-24的异位表达促进人原代CD 34+造血祖细胞和小鼠中的红细胞生成，而降低的miR-27或miR-24水平导致造血祖细胞和斑马鱼中红细胞表型受损。总之，这些数据将microRNA表达和功能整合到加塔因子协调网络中，并提供了对红细胞生成中包含GATA 1/2开关和miR-27 a/24的调控回路的机制性见解。
Transcriptional networks orchestrate complex developmental processes, and such networks are commonly instigated by master regulators for development. By now, considerable progress has been made in elucidating GATA factor-dependent genetic networks that control red blood cell development. Here we reported that GATA-1 and GATA-2 co-regulated the expression of two microRNA genes, microRNA-27a and microRNA-24, with critical roles in regulating erythroid differentiation. In general, GATA-2 occupied the miR-27a∼24 promoter and repressed their transcription in immature erythroid progenitor cells. As erythropoiesis proceeded, GATA-1 directly activated miR-27a∼24 transcription, and this involved a GATA-1-mediated displacement of GATA-2 from chromatin, a process termed ‘GATA switch’. Furthermore, the mature miR-27a and miR-24 cooperatively inhibited GATA-2 translation and favoured the occupancy switch from GATA-2 to GATA-1, thus completing a positive feedback loop to promote erythroid maturation. In line with the essential role of GATA factors, ectopic expression of miR-27a or miR-24 promoted erythropoiesis in human primary CD34+ haematopoietic progenitor cells and mice, whereas attenuated miR-27 or miR-24 level led to impaired erythroid phenotypes in haematopoietic progenitor cells and zebrafish. Taken together, these data integrated micro RNA expression and function into GATA factor coordinated networks and provided mechanistic insight into a regulatory circuit that comprised GATA1/2 switch and miR-27a/24 in erythropoiesis.
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影响因子：
37.3
作者：
Chhabra R;Dubey R;Saini N
通讯作者：
Saini N
影响因子：
2.6
作者：
Ikonomi, P;Rivera, CE;Noguchi, CT
通讯作者：
Noguchi, CT
影响因子：
2.6
作者：
Choong, Meng Ling;Yang, Henry He;McNiece, Ian
通讯作者：
McNiece, Ian
DOI：
10.1073/pnas.94.9.4487
发表时间：
1997-04-29
影响因子：
11.1
作者：
Onodera, K;Takahashi, S;Yamamoto, M
通讯作者：
Yamamoto, M
影响因子：
2.6
作者：
Kong, Kimi Y.;Owens, Kristin S.;Rogers, Jason H.;Mullenix, Jason;Velu, Chinavenmeni S.;Grimes, H. Leighton;Dahl, Richard
通讯作者：
Dahl, Richard