An MLL/COMPASS subunit functions in the XXXX dosage compensation complex to target X chromosomes for transcriptional regulation of gene expression.

@entity18040 @entity2199
Here we analyze the essential process of X-chromosome dosage compensation (DC) to elucidate mechanisms that control the assembly, genome-wide binding, and function of gene regulatory complexes that act over large chromosomal territories. We demonstrate that a subunit of @entity2199 MLL/COMPASS, a gene activation complex, acts within the DC complex ( @entity18040 ), a condensin complex, to target the @entity18040 to both X chromosomes of hermaphrodites for chromosome-wide reduction of gene expression. The @entity18040 binds to two categories of sites on X: rex (recruitment element on X) sites that recruit the @entity18040 in an autonomous, sequence-dependent manner, and dox (dependent on X) sites that reside primarily in promoters of expressed genes and bind the @entity18040 robustly only when attached to X. We find that DC mutations that abolish rex site binding greatly reduce dox site binding but do not eliminate it. Instead, binding is diminished to the low level observed at autosomal sites in wild-type animals. Changes in @entity18040 binding to these non-rex sites occur throughout development and correlate directly with transcriptional activity of adjacent genes. Moreover, autosomal @entity18040 binding is enhanced by rex site binding in cis in X-autosome fusion chromosomes. Thus, dox and autosomal sites have similar binding potential but are distinguished by linkage to rex sites. We propose a model for @entity18040 binding in which low-level @entity18040 binding at dox sites is dictated by intrinsic properties correlated with high transcriptional activity. Sex-specific @entity18040 recruitment to rex sites then enhances the magnitude of @entity18040 binding to dox sites in cis, which lack high affinity for the @entity18040 on their own. We also show that the @entity18040 balances X-chromosome gene expression between sexes by controlling transcription.
