Activation of Hox Gene Expression by Hoxa-5

Abstract

The Hox genes are expressed during embryonic development and have a role in specifying antero-posterior positional information. The genes are arranged in four clusters and a colinear relation exists between a gene's position in the cluster and its anterior boundary of expression. Genes with more anterior boundaries are also expressed earlier than genes with more posterior boundaries. Hox genes encode transcription factors; therefore, a model for the coordinate regulation of the genes within the Hox clusters is that Hox gene products regulate their own expression. To test this model, an inducible promoter was used to direct expression of exogenous Hoxa-5 in F9 embryonal carcinoma cells and the effect on endogenous Hox gene expression was measured using RNase protection assays. The production of Hoxa-5 from the expression vector activated a transient and simultaneous expression of other upstream and downstream genes of the same Hox cluster and genes from other clusters. There was an 8-hr delay between the peak of expression from the Hox vector and the endogenous Hox gene response, suggesting that Hox proteins activate other Hox genes indirectly or require additional factors which, in F9 cells, they also induce.