Human differentiation-related gene NDRG1 is a Myc downstream-regulated gene that is repressed by Myc on the core promoter region.
Human differentiation-related gene NDRG1 is a Myc downstream-regulated gene that is repressed by Myc on the core promoter region.
复制标题
人类分化相关基因NDRG1是Myc下游调控基因，在核心启动子区域被Myc抑制。
作者：
N-Myc下游调节基因1（ndrg 1）在N-Myc敲除小鼠胚胎中上调。人NDRG家族由4个高度同源的成员组成，人NDRG 1与小鼠NDRG 1具有约94%的同源性。然而，NDRG 1通过Myc抑制的调节机制尚不清楚。我们先前鉴定了人NDRG 2，并证明该基因通过与NDRG 2的核心启动子区域的Miz-1依赖性相互作用被Myc转录下调。在这里，我们提供的证据表明，人类NDRG 1是由Myc以类似于NDRG 2的方式调节。我们发现，在分化的细胞中，随着Myc表达的下降，Ndrg 1表达水平增强，但在Myc诱导后下调。结果表明，N-Myc和c-Myc均能在转录水平上抑制NDRG 1的表达。我们进一步确定了人NDRG 1的核心启动子区是Myc抑制所必需的，并验证了Myc与核心启动子区的相互作用。然而，蛋白质合成抑制剂放线菌酮的存在可以逆转Myc的抑制，表明Myc对人NDRG 1的间接抑制。此外，我们发现c-Myc介导的阻遏可以被HDACs抑制剂TSA抑制，这表明HDACs参与了阻遏过程。总之，我们的研究结果表明，与NDRG 2一样，人类NDRG 1可以通过与NDRG 1核心启动子的相互作用被Myc间接转录下调。
N-Myc downstream-regulated gene 1 (ndrg1) is up-regulated in N-Myc knockout mouse embryos. The human NDRG family consists of 4 highly homologous members and human Ndrg1 exhibits approximately 94% homology with mouse ndrg1. However, the regulatory mechanism of NDRG1 via Myc repression is as yet unknown. We previously identified human NDRG2 and demonstrated that this gene is transcriptionally down-regulated by Myc via Miz-1-dependent interaction with the core promoter region of NDRG2. Here, we provide evidence that human NDRG1 is regulated by Myc in a manner similar to NDRG2. We found that Ndrg1 expression levels were enhanced as Myc expression declined in differentiated cells, but were down-regulated following Myc induction. The data revealed that both N-Myc and c-Myc can repress human NDRG1 at the transcriptional level. We further determined that the core promoter region of human NDRG1 is required for Myc repression, and verified the interaction of Myc with the core promoter region. However, the presence of the protein synthesis inhibitor cycloheximide could reverse the repression of Myc, indicating the indirect repression of human NDRG1 by Myc. Moreover, we found that c-Myc-mediated repression can be inhibited by TSA, an HDACs inhibitor, which suggests the involvement of HDACs in the repression process. Taken together, our results demonstrate that, in common with NDRG2, human NDRG1 can be indirectly transcriptionally down-regulated by Myc via interaction with the NDRG1 core promoter.
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影响因子：
11.2
作者：
S. Kurdistani;P. Arizti;C. Reimer;M. Sugrue;S. Aaronson;S. W. Lee
通讯作者：
S. Kurdistani;P. Arizti;C. Reimer;M. Sugrue;S. Aaronson;S. W. Lee
影响因子：
64.8
作者：
O'Donnell, KA;Wentzel, EA;Mendell, JT
通讯作者：
Mendell, JT
影响因子：
14.9
作者：
LITTLEWOOD, TD;HANCOCK, DC;EVEN, GI
通讯作者：
EVEN, GI
影响因子：
11.2
作者：
Sucharita Bandyopadhyay;Sudha K. Pai;S. Gross;S. Hirota;S. Hosobe;Kunio Miura;Ken Saito;T. Commes-T.-C
通讯作者：
Sucharita Bandyopadhyay;Sudha K. Pai;S. Gross;S. Hirota;S. Hosobe;Kunio Miura;Ken Saito;T. Commes-T.-C
人类 NDRG3 基因的克隆和表达模式。
DOI：
10.1016/s0167-4781(01)00210-x
发表时间：
2001-05
期刊：
.Biochim Biophys Acta.
影响因子：
--
作者：
Zhao W;Tang R;Huang Y;Wang W;Zhou Z;Gu S;Dai J;Ying K;Xie Y;Mao Y
通讯作者：
Mao Y