PIASxbeta acts as an activator of Hoxb1 and is antagonized by Krox20 during hindbrain segmentation

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.