title: Drosophila UTX coordinates with p53 to regulate ku80 expression in response to DNA damage.
abstract: UTX is known as a general factor that activates gene transcription during development. Here, we demonstrate an additional essential role of UTX in the DNA damage response, in which it upregulates the expression of ku80 in Drosophila, both in cultured cells and in third instar larvae. We further showed that UTX mediates the expression of ku80 by the demethylation of H3K27me3 at the ku80 promoter upon exposure to ionizing radiation (IR) in a p53-dependent manner. UTX interacts physically with p53, and both UTX and p53 are recruited to the ku80 promoter following IR exposure in an interdependent manner. In contrast, the loss of utx has little impact on the expression of ku70, mre11, hid and reaper, suggesting the specific regulation of ku80 expression by UTX. Thus, our findings further elucidate the molecular function of UTX.
authors.affiliation: Institute of Life Sciences, Southeast University, State Ministry of Education Key Laboratory of Developmental Genes and Human Diseases, Nanjing, China.
authors.forename: Chengwan
authors.initials: C
authors.lastname: Zhang
authors.forename: Zehui
authors.initials: Z
authors.lastname: Hong
authors.forename: Wencui
authors.initials: W
authors.lastname: Ma
authors.forename: Da
authors.initials: D
authors.lastname: Ma
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Qian
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.forename: Feng
authors.initials: F
authors.lastname: Tie
authors.forename: Ming
authors.initials: M
authors.lastname: Fang
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics*; D001483:Base Sequence; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics* / Q000378:metabolism* / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000235:genetics* / Q000528:radiation effects; D006657:Histones / Q000378:metabolism; D000072200:Ku Autoantigen; D008745:Methylation / Q000528:radiation effects; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics / Q000528:radiation effects
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006657:Histones; D016159:Tumor Suppressor Protein p53; D010089:Oxidoreductases, N-Demethylating; C527283:UTX protein, Drosophila; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen