REGULATION OF HOXC-8 DURING MOUSE EMBRYONIC-DEVELOPMENT - IDENTIFICATION AND CHARACTERIZATION OF CRITICAL ELEMENTS INVOLVED IN EARLY NEURAL-TUBE EXPRESSION

We have characterized cis-acting elements that direct the early phase of Hoxc-8 expression using reporter gene analysis in transgenic mice. By deletion we show that a 135 bp DNA fragment, located approximately 3 kb upstream of the coding region of Hoxc-8, is capable of directing posterior neural tube expression, This early neural tube (ENT) enhance r consists of four separate elements, designated A, B, C and D, whose nucleotide sequences are similar to binding sites of known transcripti on factors. Nucleotide substitutions suggest that element A is an esse ntial component of the ENT enhancer. However element A by itself is in capable of directing neural tube expression, This element requires int eractions at any two of the other three elements, B, C or D. Thus, the components of the ENT enhancer direct neural tube expression in an in terdependent manner. We propose that Hoxc-8 is activated in the neural tube by combinatorial interactions among several proteins acting with in a small region, Our transgenic analyses provide a means to identify transcription factors that regulate Hoxc-8 expression during embryoge nesis.