Drosophila UTX coordinates with p53 to regulate ku80 expression in response to DNA damage

PLoS One. 2013 Nov 12;8(11):e78652. doi: 10.1371/journal.pone.0078652. eCollection 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Nuclear / genetics*
  • Base Sequence
  • Cell Survival / genetics
  • Cell Survival / radiation effects
  • DNA Damage*
  • DNA Repair / genetics
  • DNA Repair / radiation effects
  • DNA-Binding Proteins / genetics*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism*
  • Drosophila melanogaster / radiation effects
  • Gene Expression Regulation / genetics*
  • Gene Expression Regulation / radiation effects
  • Histones / metabolism
  • Ku Autoantigen
  • Methylation / radiation effects
  • Oxidoreductases, N-Demethylating / genetics
  • Oxidoreductases, N-Demethylating / metabolism*
  • Promoter Regions, Genetic / genetics
  • Promoter Regions, Genetic / radiation effects
  • Tumor Suppressor Protein p53 / metabolism*
  • Up-Regulation / genetics
  • Up-Regulation / radiation effects

Substances

  • Antigens, Nuclear
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Histones
  • Tumor Suppressor Protein p53
  • Oxidoreductases, N-Demethylating
  • UTX protein, Drosophila
  • Xrcc6 protein, human
  • Ku Autoantigen

Grant support

This work was supported in part by grants from the Natural Science Foundation of China (90919007 and 30900812), the New-Century Training Program Foundation for Talent of the State Education Commission and the Youth Foundation of Southeast University to Z.H. and grants from the National Basic Research Program of China (2012CB517904) and the Natural Science Foundation of China (30771068 and 31271321) to M.F. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.