[Frontiers in Bioscience 9, 24-31, January 1, 2004]

QUERKOPF, A HISTONE ACETYLTRANSFERASE, IS ESSENTIAL FOR EMBRYONIC NEUROGENESIS.

Tim Thomas and Anne K. Voss

Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

TABLE OF CONTENTS

1. Abstract
2. Introduction
3.1. Identification of a MYST family histone acetyltransferase in expressed brain development.
3.2. Protein structure of MOZ and Querkopf
3.3. Expression of Querkopf in development
3.4. Phenotype of the Querkopf gene trap mutant mice
4. Perspectives
5. Acknowledgment
6. References

1. 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.