TRANSCRIPTIONAL REGULATION DURING MAMMALIAN NEUROGENESIS

同源盒是一个183碱基对的DNA序列，最初发现于果蝇的片段和同源基因。在果蝇中，同源基因聚集在触须和双胸复合体中，统称为同源基因复合体（homc）。在小鼠基因组中，大约40个同源盒基因（Hox）聚集在四个染色体区域（Hox A至D）。Hox基因的排列顺序和前后表达模式与它们在homc中的结构同源物相同，这表明它们控制小鼠模式形成的方式与homc成员在果蝇中的作用相同。同源盒基因产物被认为是调控靶基因表达的转录因子。通过各种方法在果蝇中鉴定了一些候选靶基因，但由于现有方法的局限性，对Hox基因的靶基因知之甚少。在本研究项目中，我们通过免疫纯化天然染色质中与Hox蛋白结合的DNA序列，确定了几个候选Hox基因靶点，包括果蝇肿瘤抑制基因l (2) gl的小鼠同源物。

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.