Krox20 controls the transcription of its various targets in the developing hindbrain according to multiple modes

The zinc finger transcription factor Krox20 plays an essential role in the vertebrate hindbrain segmentation process. It positively or negatively controls a large variety of other regulatory genes, coordinating delimitation of segmental territories, specification of their identity, and maintenance of their integrity. We have investigated the molecular mechanisms of Krox20 transcriptional control by performing a detailed structure-function analysis of the protein in the developing chick hindbrain. This revealed an unsuspected diversity in the modes of action of a transcription factor in a single tissue, since regulation of each of the five tested target genes requires different parts of the protein and/or presumably different co-factors. The multiplicity of Krox20 functions might rely on this diversity. Investigation of known Krox20 co-factors was initiated in relation to this analysis. Nab was shown to act as a negative feedback modulator of the different Krox20 activating functions in the hindbrain. HCF-1 was found to bind to a Krox20 N-terminal region, which was shown to rely on multiple elements, including acidic domains, to convey Nab activation and Krox20 autoregulation.