GATA2 regulates GATA1 expression through LSD1-mediated histone modification.
GATA2 regulates GATA1 expression through LSD1-mediated histone modification.
复制标题
GATA2 通过 LSD1 介导的组蛋白修饰调节 GATA1 表达。
DOI：
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发表时间：
2016-05
影响因子：
2.2
通讯作者：
Hu Xin
中科院分区：
文献类型：
--
作者：
Guo Yidi;Fu Xueqi;Huo Bo;Wang Yongsen;Sun Jing;Meng Lingyuan;Hao Tian;Zhao Zhizhuang Joe;Hu Xin
GATA 1和GATA 2的动态和反向表达对于红系细胞的正常分化是必不可少的。我们之前的工作表明，LSD 1（一种组蛋白H3 K4脱甲基酶）在红细胞分化晚期抑制GATA 2的表达。使用K562和MEL细胞，并分别在Roswell Park Memorial Institute-1640培养基（RPMI）和Dulbecco改良Eagle培养基（DMEM）中培养。Western blot检测GATA 1、GATA 2、TAL 1、HDAC 1、HDAC 2、CoREST和β-actin蛋白的表达。采用免疫沉淀法和GST pull-down法检测沉淀蛋白复合物，并研究蛋白之间的相互作用。合成小干扰RNA（siRNA）和非特异性对照siRNA以沉默靶基因。采用免疫荧光双标法观察LSD 1与GATA 2在K562细胞中的相互作用。结果表明，敲低LSD 1基因可使K562细胞GATA 1位点H3 K4去甲基化水平升高，并激活GATA 1的表达，说明LSD 1通过介导组蛋白去甲基化抑制GATA 1的表达。在诱导K562细胞红系分化后，GATA 2和LSD 1之间的相互作用减弱，这与GATA 1表达的去抑制一致。同时，TAL 1和LSD 1之间的相互作用增加，形成有效抑制GATA 2表达的复合物。总之，这些观察结果揭示了一个优雅的机制，调节GATA 1和GATA 2的表达在红细胞分化。LSD 1主要与GATA 2形成复合物抑制造血祖细胞中的GATA 1表达，而LSD 1主要与TAL 1形成复合物抑制分化细胞中的GATA 2表达。
The dynamic and reversed expression of GATA1 and GATA2 are essential for proper erythroid differentiation. Our previous work demonstrates that LSD1, a histone H3K4 demethylase, represses GATA2 expression at late stage of erythroid differentiation. K562 and MEL cells were used and cultured in Roswell Park Memorial Institute-1640 medium (RPMI) and Dulbecco's modified Eagle's medium (DMEM), respectively. Western blot assay was used to examine the GATA1, GATA2, TAL1, HDAC1, HDAC2, CoREST and β-actin protein. The immunoprecipitation assay and GST pull-down assay were employed to detect the precipitated protein complexes and investigate the interaction between the proteins. The small interfering RNA (siRNA) and nonspecific control siRNA were synthesized to silence the target genes. Double fluorescence immunostaining was used to observe the association of LSD1 with GATA2 in K562 cells. The results indicated that knockdown of LSD1 in K562 cell causes increased H3K4 di-methylation at GATA1 locus and activates GATA1 expression, demonstrating that LSD1 represses GATA1 expression through LSD1-mediated histone demethylation. Upon induced erythroid differentiation of K562 cells, the interaction between GATA2 and LSD1 is decreased, consistent with a de-repression of GATA1 expression. Meanwhile, the interaction between TAL1 and LSD1 is increased, which forms a complex that efficiently suppresses GATA2 expression. In conclusion, these observations reveal an elegant mechanism to modulate GATA1 and GATA2 expression during erythroid differentiation. While LSD1 mainly forms complex with GATA2 to repress GATA1 expression in hematopoietic progenitor cells, it mostly forms complex with TAL1 to repress GATA2 expression in differentiated cells.
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影响因子：
2.1
作者：
Mikiko Suzuki;R. Shimizu;Masayuki Yamamoto
通讯作者：
Mikiko Suzuki;R. Shimizu;Masayuki Yamamoto
组蛋白去甲基化酶 LSD1 介导的 GATA-2 抑制对于红细胞分化至关重要。
DOI：
10.2147/dddt.s81911
发表时间：
2015
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Guo Y;Fu X;Jin Y;Sun J;Liu Y;Huo B;Li X;Hu X
通讯作者：
Hu X
影响因子：
7.7
作者：
Kerenyi MA;Shao Z;Hsu YJ;Guo G;Luc S;O'Brien K;Fujiwara Y;Peng C;Nguyen M;Orkin SH
通讯作者：
Orkin SH
影响因子：
5.3
作者：
KO LINDAJ.;J. D. Engel
通讯作者：
KO LINDAJ.;J. D. Engel
影响因子：
64.8
作者：
TSAI, FY;KELLER, G;ORKIN, SH
通讯作者：
ORKIN, SH