McCormick A, Coré N, Kerridge S, Scott M P
Department of Developmental Biology, Howard Hughes Medical Institute, Stanford University School of Medicine, CA 94305-5427, USA.
Development. 1995 Sep;121(9):2799-812. doi: 10.1242/dev.121.9.2799.
Along the anterior-posterior axis of animal embryos, the choice of cell fates, and the organization of morphogenesis, is regulated by transcription factors encoded by clustered homeotic or 'Hox' genes. Hox genes function in both epidermis and internal tissues by regulating the transcription of target genes in a position- and tissue-specific manner. Hox proteins can have distinct targets in different tissues; the mechanisms underlying tissue and homeotic protein specificity are unknown. Light may be shed by studying the organization of target gene enhancers. In flies, one of the target genes is teashirt (tsh), which encodes a zinc finger protein. tsh itself is a homeotic gene that controls trunk versus head development. We identified a tsh gene enhancer that is differentially activated by Hox proteins in epidermis and mesoderm. Sites where Antennapedia (Antp) and Ultrabithorax (Ubx) proteins bind in vitro were mapped within evolutionarily conserved sequences. Although Antp and Ubx bind to identical sites in vitro, Antp activates the tsh enhancer only in epidermis while Ubx activates the tsh enhancer in both epidermis and in somatic mesoderm. We show that the DNA elements driving tissue-specific transcriptional activation by Antp and Ubx are separable. Next to the homeotic protein-binding sites are extensive conserved sequences likely to control tissue activation by different homeodomain proteins. We propose that local interactions between homeotic proteins and other factors effect activation of targets in proper cell types.
在动物胚胎的前后轴上，细胞命运的选择以及形态发生的组织是由成簇的同源异型或“Hox”基因编码的转录因子调控的。Hox基因通过以位置和组织特异性方式调控靶基因的转录，在表皮和内部组织中发挥作用。Hox蛋白在不同组织中可能有不同的靶标；组织和同源异型蛋白特异性的潜在机制尚不清楚。研究靶基因增强子的组织方式可能会有所启发。在果蝇中，一个靶基因是teashirt（tsh），它编码一种锌指蛋白。tsh本身是一个控制躯干与头部发育的同源异型基因。我们鉴定出一个tsh基因增强子，它在表皮和中胚层中被Hox蛋白差异激活。触角足蛋白（Antp）和超双胸蛋白（Ubx）在体外结合的位点在进化保守序列中被定位。尽管Antp和Ubx在体外结合相同的位点，但Antp仅在表皮中激活tsh增强子，而Ubx在表皮和体中胚层中均激活tsh增强子。我们表明，驱动Antp和Ubx组织特异性转录激活的DNA元件是可分离的。在同源异型蛋白结合位点旁边是广泛的保守序列，可能控制不同同源结构域蛋白的组织激活。我们提出，同源异型蛋白与其他因子之间的局部相互作用影响在适当细胞类型中靶标的激活。
