A p53-bound enhancer region controls a long intergenic noncoding RNA required for p53 stress response

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Melo, CA (Author) Other; Leveille, N (Author) Other; Rooijers, K (Author) Other; Wijchers, PJ (Author) Other; Geeven, G (Author) Other; Tal, A (Author) Other; Melo, SA (Author) FMUP; de Laat, W (Author) Other; Agami, R (Author) Other

Journal

Title: Oncogene

Vol. 35

Pages: 4399-4406

ISSN: 0950-9232

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 17 Citations

Scopus - 17 Citations

Other information

Authenticus ID: P-00K-W0N

DOI: 10.1038/onc.2015.502

Abstract (EN): Genome-wide chromatin studies identified the tumor suppressor p53 as both a promoter and an enhancer-binding transcription factor. As an enhancer factor, p53 can induce local production of enhancer RNAs, as well as transcriptional activation of distal neighboring genes. Beyond the regulation of protein-coding genes, p53 has the capacity to regulate long intergenic noncoding RNA molecules (lincRNAs); however, their importance to the p53 tumor suppressive function remains poorly characterized. Here, we identified and characterized a novel p53-bound intronic enhancer that controls the expression of its host, the lincRNA00475 (linc-475). We demonstrate the requirement of linc-475 for the proper induction of a p53-dependent cell cycle inhibitory response. We further confirm the functional importance of linc-475 in the maintenance of CDKN1A/p21 levels, a cell cycle inhibitor and a major p53 target gene, following p53 activation. Interestingly, loss of linc-475 reduced the binding of both p53 and RNA polymerase II (RNAPII) to the promoter of p21, attenuating its transcription rate following p53 activation. Altogether, our data suggest a direct role of p53-bound enhancer domains in the activation of lincRNAs required for an efficient p53 transcriptional response.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8