SRA

We report the direct target genes of ATF4 and CHOP in response to endoplasim reticulum stress through next generation sequencing. By obtaining genowide sequence from chromatin immunoprecipitated DNA with anti-CHOP and anit-ATF4, we identified direct binding sites of ATF4 and CHOP in promoter regions of their target genes in mouse embrynic fibroblasts (MEFs) in response to ER stress. In addition, we obtained list of genes which are differentially regulated in Atf4 or Chop-deficient MEFs compared to the wild-type MEFs in response to ER stress. We found that genes related with unfolded protein response and protein synthesis were directly regulated by ATF4 and CHOP. Through this observation, we conclude that main role of ATF4 and CHOP as transcription factors is to enhance mRNA translation in respone to ER stress. This sutdy provide new insight of genetic network of ATF4 and CHOP in response to ER stress. Overall design: For ChIP-seq, Chop+/+ and Chop-/- MEFs were treated with Tunicamycin, N-glycosylation inhibitor, to induce ER stress for 8hr. Atf4+/+ and Atf4-/- MEFs were also treated same condition for ChIP-Seq. For mRNA-seq, wild-type, Atf4-/-, and Chop-/- MEFs were treated with tunicamycin for 8hr for experiments.