Combinatorial clustering of distinct DNA motifs directs synergistic binding of Caenorhabditis elegans dosage compensation complex to X chromosomes

Significance Diverse regulatory mechanisms balance X-chromosome gene expression between sexes in mammals, fruit flies, and nematodes (XY/XO males and XX females/hermaphrodites). We identify DNA motifs on X that recruit dosage compensation complexes (DCCs) in nematode hermaphrodites to reduce X-chromosome expression. Recruitment sites on X, but not regions on autosomes, contain diverse combinations of different motifs or multiple copies of one motif. DCC binding studies in vivo and in vitro of wild-type and mutant X-recruitment sites validate motif usage. We find that clustering of motifs in different combinations with appropriate orientation and spacing promotes synergy in DCC binding, thereby triggering DCC assembly specifically along X. We demonstrate how regulatory complexes can be recruited across an entire chromosome to control its gene expression.