title: Identification and analysis of large intergenic non-coding RNAs regulated by p53 family members through a genome-wide analysis of p53-binding sites.
abstract: p53 is one of the most important known tumor suppressor genes, and it is inactivated in approximately half of human cancers. p53 family members execute various functions, such as apoptosis induction and cell cycle arrest, by modulating transcriptional regulation. Therefore, the direct transcriptional targets of the p53 family must be explored to elucidate the functional mechanisms of family members. To identify the direct transcriptional targets of p53 family members, we performed chromatin immunoprecipitation together with next-generation sequencing (ChIP-seq) and searched for p53-binding motifs across the entire human genome. Among the identified ChIP-seq peaks, approximately half were located in an intergenic region. Therefore, we assumed large intergenic non-coding RNAs (lincRNAs) to be major targets of the p53 family. Recent reports have revealed that lincRNAs play an important role in various biological and pathological processes, such as development, differentiation, stemness and carcinogenesis. Through a combination of ChIP-seq and in silico analyses, we found 23 lincRNAs that are upregulated by the p53 family. Additionally, knockdown of specific lincRNAs modulated p53-induced apoptosis and promoted the transcription of a gene cluster. Our results suggest that p53 family members, and lincRNAs constitute a complex transcriptional network involved in various biological functions and tumor suppression.
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine and.
authors.forename: Masashi
authors.initials: M
authors.lastname: Idogawa
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ohashi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Reo
authors.initials: R
authors.lastname: Maruyama
authors.forename: Lisa
authors.initials: L
authors.lastname: Kashima
authors.forename: Hiromu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Takashi
authors.initials: T
authors.lastname: Tokino
mesh_terms: D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D021901:DNA, Intergenic; D015894:Genome, Human; D006801:Humans; D005810:Multigene Family; D011485:Protein Binding; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D021901:DNA, Intergenic; D062085:RNA, Long Noncoding; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53