During vertebrate development, the temporal control of Hox gene transcriptional activation follows the genomic order of the genes within the Hox clusters. Although it is recognized that this "Hox clock" serves to coordinate body patterning, the underlying mechanism remains elusive. We have shown that successive Hox gene activation in the mouse embryo is closely associated with a directional transition in chromatin status, as judged by the dynamic progression of transcription-competent modifications: Increases in activation marks correspond to decreases in repressive marks. Furthermore, using a mouse in which a Hox cluster was split into two pieces, we document the necessity to maintain a clustered organization to properly implement this process. These results suggest that chromatin modifications are important parameters in the temporal regulation of this gene family.