title: Identification of chromatin-associated regulators of MSL complex targeting in Drosophila dosage compensation.
abstract: Sex chromosome dosage compensation in Drosophila provides a model for understanding how chromatin organization can modulate coordinate gene regulation. Male Drosophila increase the transcript levels of genes on the single male X approximately two-fold to equal the gene expression in females, which have two X-chromosomes. Dosage compensation is mediated by the Male-Specific Lethal (MSL) histone acetyltransferase complex. Five core components of the MSL complex were identified by genetic screens for genes that are specifically required for male viability and are dispensable for females. However, because dosage compensation must interface with the general transcriptional machinery, it is likely that identifying additional regulators that are not strictly male-specific will be key to understanding the process at a mechanistic level. Such regulators would not have been recovered from previous male-specific lethal screening strategies. Therefore, we have performed a cell culture-based, genome-wide RNAi screen to search for factors required for MSL targeting or function. Here we focus on the discovery of proteins that function to promote MSL complex recruitment to "chromatin entry sites," which are proposed to be the initial sites of MSL targeting. We find that components of the NSL (Non-specific lethal) complex, and a previously unstudied zinc-finger protein, facilitate MSL targeting and display a striking enrichment at MSL entry sites. Identification of these factors provides new insight into how MSL complex establishes the specialized hyperactive chromatin required for dosage compensation in Drosophila.
authors: Department of Molecular Biology, Cellular Biology, and Biochemistry, Brown University, Providence, Rhode Island, USA.
authors: Erica
authors: E
authors: Larschan
authors: Marcela M L
authors: MM
authors: Soruco
authors: Ok-Kyung
authors: OK
authors: Lee
authors: Shouyong
authors: S
authors: Peng
authors: Eric
authors: E
authors: Bishop
authors: Jessica
authors: J
authors: Chery
authors: Karen
authors: K
authors: Goebel
authors: Jessica
authors: J
authors: Feng
authors: Peter J
authors: PJ
authors: Park
authors: Mitzi I
authors: MI
authors: Kuroda
mesh_terms: D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004303:Dosage Compensation, Genetic; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics; D034622:RNA Interference; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D033921:Vesicular Transport Proteins; D014960:X Chromosome / Q000235:genetics*
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C553663:NSL1 protein, Drosophila; D009687:Nuclear Proteins; D014157:Transcription Factors; D033921:Vesicular Transport Proteins; C082132:msl-1 protein, Drosophila