Bhlhb5 and Prdm8 form a repressor complex involved in neuronal circuit assembly.
Bhlhb5 and Prdm8 form a repressor complex involved in neuronal circuit assembly.
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DOI：
10.1016/j.neuron.2011.09.035
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发表时间：
2012-01-26
期刊：
影响因子：
16.2
通讯作者：
Greenberg ME
中科院分区：
文献类型：
--
作者：
Ross SE;McCord AE;Jung C;Atan D;Mok SI;Hemberg M;Kim TK;Salogiannis J;Hu L;Cohen S;Lin Y;Harrar D;McInnes RR;Greenberg ME
虽然抑制基因表达的转录因子在神经系统发育中起着关键作用，但其作用机制仍有待了解。在这里，我们报告说，寡核苷酸相关的转录因子Bhlhb 5（也称为Bhlhe 22）形成一个阻遏复合物与PR/SET结构域蛋白，Prdm 8。我们发现，Bhlhb 5结合到序列特异性DNA元件，然后招募Prdm 8，介导靶基因的抑制。这种相互作用对于阻遏物功能至关重要，因为缺乏Bhlhb 5或Prdm 8的小鼠具有惊人相似的细胞和行为表型，包括端脑背侧神经元的轴突错误定位和异常瘙痒样行为。我们提供的证据表明，钙粘蛋白-11的功能作为一个目标的Prdm 8/Bhlhb 5阻遏复合物，必须抑制适当的神经元发育发生。这些发现表明Prdm 8是Bhlhb 5的专性伴侣，形成一种抑制复合物，部分通过对钙粘蛋白-11的精确调节来指导神经发育。
Although transcription factors that repress gene expression play critical roles in nervous system development, their mechanism of action remains to be understood. Here we report that the Olig-related transcription factor Bhlhb5 (also known as Bhlhe22) forms a repressor complex with the PR/SET domain protein, Prdm8. We find that Bhlhb5 binds to sequence-specific DNA elements and then recruits Prdm8, which mediates the repression of target genes. This interaction is critical for repressor function since mice lacking either Bhlhb5 or Prdm8 have strikingly similar cellular and behavioral phenotypes, including axonal mistargeting by neurons of the dorsal telencephalon and abnormal itch-like behavior. We provide evidence that Cadherin-11 functions as a target of the Prdm8/Bhlhb5 repressor complex that must be repressed for proper neuronal development to occur. These findings suggest that Prdm8 is an obligate partner of Bhlhb5, forming a repressor complex that directs neural development in part through the precise regulation of Cadherin-11.
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