Drosophila Dosage Compensation Loci Associate with a Boundary-Forming Insulator Complex

Abstract

CES (chromatin entry sites) are 100-1,500 bp elements that recruit MSL (Male Specific Lethal) complexes to the X-chromosome to upregulate expression of X-linked genes in male flies. CES contain one or more ∼20 bp GA rich sequences called MREs (MSL recognition elements) that are critical for dosage compensation. Recent studies indicate that CES also correspond to boundaries of X-chromosomal TADs (topologically associated domains). Here we show that a ∼1,000 kDa complex called the LBC, which is required for the functioning of the Bithorax complex boundary Fab-7, interacts specifically with a special class of CES that contain multiple MREs. Mutations in the MRE sequences of three of these CES that disrupt function in vivo abrogate interactions with the LBC. Moreover, reducing the levels of two LBC components compromises MSL recruitment. Finally, we show that several of the CES that are physically linked to each other in vivo are LBC interactors.