Zheng Sanduo, Villa Raffaella, Wang Jia, Feng Yingang, Wang Jinfeng, Becker Peter B, Ye Keqiong
Department of Biochemistry and Molecular Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, China; National Institute of Biological Sciences, Beijing 102206, China;
Molecular Biology Unit, Adolf Butenandt Institute, Center for Integrated Protein Science, Ludwig-Maximilians University, 80336 Munich, Germany;
Genes Dev. 2014 Dec 1;28(23):2652-62. doi: 10.1101/gad.250936.114.
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.
雄性特异性致死剂量补偿复合体（MSL-DCC）在果蝇雄性个体中选择性地组装在X染色体上，并通过组蛋白乙酰化使基因转录激活两倍。一个MSL识别元件（MRE）序列基序引发了最初的MSL结合，但它是如何被识别的仍不清楚。在这里，我们鉴定出MSL2的CXC结构域特异性识别MRE基序，并确定了其与特异性和非特异性DNA结合的晶体结构。CXC结构域主要与DNA双链的一条链接触，并利用单个精氨酸从小沟中直接读出二核苷酸序列。当与非特异性序列结合时，精氨酸是灵活的。MRE基序的核心区域在相反链上有两个结合位点，可协同招募一个CXC二聚体。MSL2的特异性DNA结合突变体在体内的MRE结合和X染色体定位方面受损。我们的结果揭示了CXC结构域的多种动态DNA结合模式，这些模式将MSL-DCC靶向到X染色体上。
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