title: Microarray and ChIP-seq data analysis revealed changes in p53-mediated transcriptional regulation in Nutlin-3-treated U2OS cells.
abstract: Integrative analysis of chromatin immunoprecipitation-sequencing (ChIP-seq) data and microarray data was performed to illustrate the effect of Nutlin‑3 on promoter selectivity and transcriptional regulation by the tumor suppressor p53 in U2OS human osteosarcoma cells. Raw data (accession number, GSE46642) were downloaded from Gene Expression Omnibus. Differential analyses were performed using package limma of R software. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed for the differentially expressed genes (DEGs) using the Database for Annotation, Visualization and Integration Discovery. Integrative analysis of ChIP‑seq data and microarray data were confirmed with ChIP‑Array. A total of 565 DEGs were identified, including 373 upregulated genes and 192 downregulated genes. Genes involved in the p53 signaling pathway, cell cycle, DNA replication, cytokine‑cytokine receptor interaction and melanoma were markedly over‑represented in the DEGs. A total of 39 DEGs were directly regulated by p53 and two were the transcription factors (TFs), E2F2 and HOXA1. E2F2 regulated 25 DEGs, while HOXA1 regulated one DEG. The cell cycle, p53 signaling pathway, melanoma and pathways involved in cancer were enriched in the direct and indirect target genes. Changes in the p53‑binding pattern induced by Nutlin‑3 were described in the present study, which may advance the understanding of the regulatory network of p53 in osteosarcoma and aid in the development of novel therapies.
authors.affiliation: Department of Spinal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Song
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Spinal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Niu
authors.affiliation: Department of Medical Records, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Chang-Yan
authors.initials: CY
authors.lastname: Xu
authors.affiliation: Department of Spinal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Spinal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Gui-Bin
authors.initials: GB
authors.lastname: Bi
authors.affiliation: Department of Spinal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Spinal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gong
authors.affiliation: Department of Spinal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Tian
authors.affiliation: Department of Spinal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Tian-Hong
authors.initials: TH
authors.lastname: Nie
mesh_terms: D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D010879:Piperazines / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D059467:Transcriptome; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D007093:Imidazoles; D010879:Piperazines; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C482205:nutlin 3