Garcia-Dominguez Mario, Gilardi-Hebenstreit Pascale, Charnay Patrick
INSERM, U 784, Ecole Normale Supérieure, Paris, France.
EMBO J. 2006 Jun 7;25(11):2432-42. doi: 10.1038/sj.emboj.7601122. Epub 2006 May 4.
The zinc-finger transcription factor Krox20 constitutes a key regulator of hindbrain development, essential for the formation and specification of rhombomeres (r) 3 and 5. It is in particular responsible for the respective activation and repression of odd- and even-numbered rhombomere-specific genes, which include Hox genes. In this study, we have identified PIASxbeta as a novel direct interactor of Krox20. In addition, we found that PIASxbeta is able to activate the r4-specific gene Hoxb1. Binding of Krox20 prevents this activation, providing a molecular basis for the repression of Hoxb1 by Krox20. The same domain in the Krox20 protein, the zinc-fingers, is involved in DNA binding for transcriptional activation and in interaction with PIASxbeta for transcriptional repression, although the actual precise contacts are different. Our findings add an additional level in the complexity of Hox gene regulation and provide an example of how a single regulator can coordinate the activation and repression of a set of genes by very different mechanisms, acting as a molecular switch to specify cell identity and fate.
锌指转录因子Krox20是后脑发育的关键调节因子，对菱脑节（r）3和5的形成及特化至关重要。它尤其负责奇数和偶数菱脑节特异性基因（包括Hox基因）的激活与抑制。在本研究中，我们鉴定出PIASxbeta是Krox20新的直接相互作用蛋白。此外，我们发现PIASxbeta能够激活r4特异性基因Hoxb1。Krox20的结合会阻止这种激活，为Krox20对Hoxb1的抑制提供了分子基础。Krox20蛋白中的同一结构域，即锌指，虽然实际的精确接触不同，但它既参与转录激活的DNA结合，也参与与PIASxbeta的转录抑制相互作用。我们的研究结果增加了Hox基因调控的复杂性，并提供了一个例子，说明单个调节因子如何通过非常不同的机制协调一组基因的激活和抑制，作为分子开关来确定细胞身份和命运。
