title: Structural basis of X chromosome DNA recognition by the MSL2 CXC domain during Drosophila dosage compensation.
abstract: The male-specific lethal dosage compensation complex (MSL-DCC) selectively assembles on the X chromosome in Drosophila males and activates gene transcription by twofold through histone acetylation. An MSL recognition element (MRE) sequence motif nucleates the initial MSL association, but how it is recognized remains unknown. Here, we identified the CXC domain of MSL2 specifically recognizing the MRE motif and determined its crystal structure bound to specific and nonspecific DNAs. The CXC domain primarily contacts one strand of DNA duplex and employs a single arginine to directly read out dinucleotide sequences from the minor groove. The arginine is flexible when bound to nonspecific sequences. The core region of the MRE motif harbors two binding sites on opposite strands that can cooperatively recruit a CXC dimer. Specific DNA-binding mutants of MSL2 are impaired in MRE binding and X chromosome localization in vivo. Our results reveal multiple dynamic DNA-binding modes of the CXC domain that target the MSL-DCC to X chromosomes.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, China; National Institute of Biological Sciences, Beijing 102206, China;
authors.forename: Sanduo
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Molecular Biology Unit, Adolf Butenandt Institute, Center for Integrated Protein Science, Ludwig-Maximilians University, 80336 Munich, Germany;
authors.forename: Raffaella
authors.initials: R
authors.lastname: Villa
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, China; National Institute of Biological Sciences, Beijing 102206, China;
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Qingdao Engineering Laboratory of Single Cell Oil, Shandong Provincial Key Laboratory of Energy Genetics, Qingdao Institute of BioEnergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shangdong 266101, China;
authors.forename: Yingang
authors.initials: Y
authors.lastname: Feng
authors.affiliation: National Laboratory of Biomacromolecules.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Molecular Biology Unit, Adolf Butenandt Institute, Center for Integrated Protein Science, Ludwig-Maximilians University, 80336 Munich, Germany;
authors.forename: Peter B
authors.initials: PB
authors.lastname: Becker
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China; Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China yekeqiong@nibs.ac.cn.
authors.forename: Keqiong
authors.initials: K
authors.lastname: Ye
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004303:Dosage Compensation, Genetic; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000378:metabolism*; D014960:X Chromosome / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C094166:msl-2 protein, Drosophila
keywords: DNA–protein complex; crystal structure; dosage compensation; nonspecific DNA binding