TRANSCRIPTIONAL REGULATION DURING MAMMALIAN NEUROGENESIS

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The homeobox is a 183-base-pare DNA sequence originally found in Drosophila segmentation and homeotic genes. InDrosophila, homeotic genes are clustered in the Antennapedia and Bithorax complexes, collectively called the homeotic gene coplex (HOM-C). In the mouse genome, about 40 homeobox genes (Hox) are clustered in four chromosomal regions (Hox A to D). The Hox genes are arranged in the same order and have the same antero-posterior patten of expression as thier structural homologue in the HOM-C,suggesting that they control mouse pattern formation in the same way that HOM-C members do in Drosophila. Homeobox gene products are believed to be transcription factors that regulate expression of target genes. A few candidate target genes have been identified in Drosophila by various approaches but the Hox gene targets are poorly understood, mostly because of limitations in the available approaches. In this research project we identify several candidate Hox gene targets, including a mouse homologue if the Drosophila tumor-suppressor gene l (2) gl, by immunopurification of DNA sequences bound to a Hox protein in native chromatin.