例如:"lncRNA", "apoptosis", "WRKY"

Genome-wide profiling of p53-regulated enhancer RNAs uncovers a subset of enhancers controlled by a lncRNA.

Nat Commun. 2015 Mar 27;6:6520
Nicolas Léveillé 1 , Carlos A Melo 2 , Koos Rooijers 1 , Angel Díaz-Lagares 3 , Sonia A Melo 4 , Gozde Korkmaz 1 , Rui Lopes 1 , Farhad Akbari Moqadam 5 , Ana R Maia 6 , Patrick J Wijchers 7 , Geert Geeven 7 , Monique L den Boer 5 , Raghu Kalluri 4 , Wouter de Laat 7 , Manel Esteller 8 , Reuven Agami 9
Nicolas Léveillé 1 , Carlos A Melo 2 , Koos Rooijers 1 , Angel Díaz-Lagares 3 , Sonia A Melo 4 , Gozde Korkmaz 1 , Rui Lopes 1 , Farhad Akbari Moqadam 5 , Ana R Maia 6 , Patrick J Wijchers 7 , Geert Geeven 7 , Monique L den Boer 5 , Raghu Kalluri 4 , Wouter de Laat 7 , Manel Esteller 8 , Reuven Agami 9
+ et al

[No authors listed]

Author information
  • 1 Division of Biological Stress Response, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
  • 2 Doctoral Programme in Biomedicine and Experimental Biology, Centre for Neuroscience and Cell Biology, Coimbra University, 3004-504 Coimbra, Portugal.
  • 3 Division of Cancer Epigenetics, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Catalonia 08908, Spain.
  • 4 Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA.
  • 5 Department of Pediatric Oncology and Hematology, Erasmus University Medical Center, Erasmus MC, 3015 CE Rotterdam, The Netherlands.
  • 6 Department of Cell Biology and Cancer Genomics Center, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
  • 7 Hubrecht Institute-KNAW, University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, The Netherlands.
  • 8 Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia 08010, Spain.
  • 9 Erasmus MC, Rotterdam University, 3000 CA Rotterdam, The Netherlands.

摘要


p53 binds enhancers to regulate key target genes. Here, we globally mapped p53-regulated enhancers by looking at enhancer RNA (eRNA) production. Intriguingly, while many p53-induced enhancers contained p53-binding sites, most did not. As long non-coding RNAs (lncRNAs) are prominent regulators of chromatin dynamics, we hypothesized that p53-induced lncRNAs contribute to the activation of enhancers by p53. Among p53-induced lncRNAs, we identified LED and demonstrate that its suppression attenuates p53 function. Chromatin-binding and eRNA expression analyses show that LED associates with and activates strong enhancers. One prominent target of LED was located at an enhancer region within CDKN1A gene, a potent p53-responsive cell cycle inhibitor. LED knockdown reduces CDKN1A enhancer induction and activity, and cell cycle arrest following p53 activation. Finally, promoter-associated hypermethylation analysis shows silencing of LED in human tumours. Thus, our study identifies a new layer of complexity in the p53 pathway and suggests its dysregulation in cancer.

原始数据


 保存测序数据
Sample name
Organism Experiment title Sample type Library instrument Attributes
cell linechirp pool probe sequencessource name
MCF7 GROseq nutlin 2
Homo sapiens GSM1422218: MCF7 GROseq nutlin 2; Homo sapiens; OTHER OTHER Illumina HiSeq 2000 MCF7 mammary gland/breast
MCF7 GROseq nutlin 1
Homo sapiens GSM1422217: MCF7 GROseq nutlin 1; Homo sapiens; OTHER OTHER Illumina HiSeq 2000 MCF7 mammary gland/breast
MCF7 GROseq control 2
Homo sapiens GSM1422216: MCF7 GROseq control 2; Homo sapiens; OTHER OTHER Illumina HiSeq 2000 MCF7 mammary gland/breast
MCF7 GROseq control 1
Homo sapiens GSM1422215: MCF7 GROseq control 1; Homo sapiens; OTHER OTHER Illumina HiSeq 2000 MCF7 mammary gland/breast
MCF7 p21ekd siep21e 2
Homo sapiens GSM1294988: MCF7 p21ekd siep21e 2; Homo sapiens; RNA-Seq RNA-Seq Illumina HiSeq 2000 MCF7 mammary gland/breast