The spatial folding of chromatin has been proposed to be involved in the 
regulation and coordination of gene expression. The mammalian Hox gene clusters 
form a particularly interesting case of coordinated gene regulation. Within each 
Hox cluster, the linear order of the genes closely reflects their temporal and 
anatomical expression pattern. This striking phenomenon suggests that the 
overall structure of the Hox clusters is important for their regulation. Recent 
studies employing chromatin conformation capture techniques indicate that Hox 
clusters adopt a remarkable spatial configuration, in which active and inactive 
genes are segregated into two distinct chromatin compartments. Here we discuss 
the possible underlying mechanisms and regulatory roles of this spatial 
compartmentalization.