Querkopf, a histone acetyltransferase, is essential for embryonic neurogenesis.

Abstract

DNA binding transcription factors require the presence of co-activators in order to exert their effects on the pattern of gene expression in a cell. An essential element of co-activator complexes is one or more proteins that have histone acetyltransferase activity. In a gene trap screen for mutations affecting brain development, we identified a member of the MYST family histone acetyltransferases, Querkopf. Querkopf is the mouse homologue of the human protein MORF and both these proteins are closely related to MOZ. Querkopf shows a dynamic pattern of expression in the telencephalon. It is initially expressed strongly in the dorsal telencephalon and then in the ventral telencephalon. This suggests that, unusually for a histone acetyltransferase, part of its activity is regulated at the transcriptional level. Mice carrying a mutation in the querkopf gene have defects in the development of the cerebral cortex. At all stages of fetal development querkopf mutant mice show a reduced number of cells in the cortical plate resulting in a reduction in the size of the adult cortex. The adult cortex in these mice contains less large pyramidal cells and a reduced number of interneurons. In addition Querkopf is also involved in adult neurogenesis. In this short review we examine the role of co-activators of transcription in general and the function of Querkopf in particular.