title: The common stress responsive transcription factor ATF3 binds genomic sites enriched with p300 and H3K27ac for transcriptional regulation.
abstract: Dysregulation of the common stress responsive transcription factor ATF3 has been causally linked to many important human diseases such as cancer, atherosclerosis, infections, and hypospadias. Although it is believed that the ATF3 transcription activity is central to its cellular functions, how ATF3 regulates gene expression remains largely unknown. Here, we employed ATF3 wild-type and knockout isogenic cell lines to carry out the first comprehensive analysis of global ATF3-binding profiles in the human genome under basal and stressed (DNA damage) conditions.
  
  
  
  Although expressed at a low basal level, ATF3 was found to bind a large number of genomic sites that are often associated with genes involved in cellular stress responses. Interestingly, ATF3 appears to bind a large portion of genomic sites distal to transcription start sites and enriched with p300 and H3K27ac. Global gene expression profiling analysis indicates that genes proximal to these genomic sites were often regulated by ATF3. While DNA damage elicited by camptothecin dramatically altered the ATF3 binding profile, most of the genes regulated by ATF3 upon DNA damage were pre-bound by ATF3 before the stress. Moreover, we demonstrated that ATF3 was co-localized with the major stress responder p53 at genomic sites, thereby collaborating with p53 to regulate p53 target gene expression upon DNA damage.
  
  
  
  These results suggest that ATF3 likely bookmarks genomic sites and interacts with other transcription regulators to control gene expression.
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Georgia Cancer Center, Augusta University, Augusta, GA, USA.
authors.forename: Xingyao
authors.initials: X
authors.lastname: Li
authors.affiliation: Center for Cell Biology and Cancer Research, Albany Medical College, Albany, NY, USA.
authors.forename: Mingxiong
authors.initials: M
authors.lastname: Guo
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. jindan-yu@northwestern.edu.
authors.forename: Jindan
authors.initials: J
authors.lastname: Yu
authors.affiliation: Georgia Cancer Center, Augusta University, Augusta, GA, USA. cyan@augusta.edu.|Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA, USA. cyan@augusta.edu.|Center for Cell Biology and Cancer Research, Albany Medical College, Albany, NY, USA. cyan@augusta.edu.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Yan
mesh_terms: D051700:Activating Transcription Factor 3 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D001665:Binding Sites / Q000187:drug effects; D002166:Camptothecin / Q000494:pharmacology; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D055786:Gene Knockout Techniques; D045325:HCT116 Cells; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D051700:Activating Transcription Factor 3; D002166:Camptothecin; D004247:DNA; D006657:Histones; D016159:Tumor Suppressor Protein p53; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C490449:ATF3 protein, human; C495901:TP53 protein, human
keywords: ATF3; ChIP-seq; Enhancer; H3K27ac; p300; p53