Synergistic interactions between MSL complex and the CLAMP protein regulate Drosophila dosage compensation

In heterogametic species, the process of dosage compensation is required to equalize transcript levels between the sex chromosomes in males and females. The Drosophila Male-Specific Lethal (MSL) complex increases transcript levels on the single male X-chromosome to equal the transcript levels in XX females. However, the mechanism by which dosage compensation is targeted to the male X-chromosome is not understood because neither the MSL complex nor cis-acting DNA sequences are sufficient. Using chromatin immunoprecipitation (ChIP) followed by high-throughput sequencing (ChIP-seq) we demonstrate that a previously unstudied zinc-finger protein, CLAMP (Chromatin-Linked Adaptor for MSL Proteins), regulates X-chromosome specificity. CLAMP tethers MSL complex to the X-chromosome and exhibits a synergistic interaction with MSL complex that increases X-chromosome specificity. Also, CLAMP is highly enriched at likely "seed" sites prior to MSL complex recruitment. The discovery of CLAMP identifies a key factor that regulates the chromosome-specific targeting of dosage compensation and provides new insights into how sub-nuclear domains of coordinate gene regulation are formed within complex genomes.