Ultraconserved Sequences Associated with HoxD Cluster Have Strong Repression Activity

Increase in the complexity of organisms during evolution strongly correlates with the increase in the noncoding DNA content of their genomes. Although a gradual increase in the proportion of repetitiveDNAelements alongwith increasing complexity is known, most of the noncoding components of the genome remain uncharacterized. A nonrepetitive but highly conserved noncoding component of the genome in vertebrates, called ultraconserved DNA sequences, constitutes up to 5% of the human genome. The function of most of the ultraconserved DNA elements is notwell known. One such ultraconserved stretch of DNA has been identified upstream of the HoxD cluster in vertebrates. We analyzed the function of these elements in different cell lines and zebrafish. Our results suggest that these ultraconserved sequenceswork as repressor elements. This is the first reportwhich reveals the repressor function of ultraconserved sequences and implicates their role in the regulation of developmental genes.