M. Kmita et al., Mechanisms of Hox gene colinearity: transposition of the anterior Hoxb1 gene into the posterior HoxD complex, GENE DEV, 14(2), 2000, pp. 198-211
Transposition of Herd genes to a more posterior (5') location within the Ho
xD complex suggested that colinearity in the expression of these genes was
due, in part, to the existence of a silencing mechanism originating at the
5' end of the cluster and extending towards the 3' direction. To assess the
strength and specificity of this repression, as well as to challenge avail
able models on colinearity, we inserted a Hoxb1/lacZ transgene within the p
osterior HoxD complex, thereby reconstructing a cluster with a copy of the
most anterior gene inserted at the most posterior position. Analysis of Hox
b1 expression after ectopic relocation revealed that Hoxb1-specific activit
y in the fourth rhombomere was totally abolished. Treatment with retinoic a
cid, or subsequent relocations toward more 3' positions in the HoxD complex
, did not release this silencing in hindbrain cells. In contrast, however,
early and anterior transgene expression in the mesoderm was unexpectedly no
t suppressed. Furthermore, the transgene induced a transient ectopic activa
tion of the neighboring Hoxd13 gene, without affecting other genes of the c
omplex. Such a local and transient break in colinearity was also observed a
fter transposition of the Hoxd9/lacZ reporter gene, indicating that it may
be a general property of these transgenes when transposed at an ectopic loc
ation. These results are discussed in the context of existing models, which
account for colinear activation of vertebrate Hox genes.