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

Oncogene
Carlos A MeloReuven Agami

Abstract

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 p...Continue Reading

References

Jul 2, 1992·Nature·D P Lane
Aug 29, 1995·Proceedings of the National Academy of Sciences of the United States of America·M L AgarwalG R Stark
Dec 12, 2001·Trends in Biochemical Sciences·K Rippe
Feb 16, 2002·Science·Job DekkerNancy Kleckner
Jul 1, 2009·Cell·Jennifer E Phillips, Victor G Corces
Apr 16, 2010·Nature·Tae-Kyung KimMichael E Greenberg
May 21, 2010·PLoS Biology·Francesca De SantaGioacchino Natoli
Mar 29, 2011·Nature·Jason ErnstBradley E Bernstein
Sep 29, 2011·The EMBO Journal·Erik Splinter, Wouter de Laat
Jun 6, 2012·Annual Review of Biochemistry·John L Rinn, Howard Y Chang
Jan 1, 2013·Molecular Cell·Carlos A MeloReuven Agami
Jan 31, 2013·Nature Biotechnology·Seung Woo ChoJin-Soo Kim
Jun 14, 2013·Aging Cell·Kotb AbdelmohsenMyriam Gorospe
Dec 18, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jessica ZuinKerstin S Wendt
Mar 13, 2014·Nature Reviews. Genetics·Daria ShlyuevaAlexander Stark
Jul 31, 2014·Nature Methods·Neville E SanjanaFeng Zhang
Sep 30, 2014·Molecular Cell·Katie SchaukowitchTae-Kyung Kim
Jul 22, 2015·Biochimica Et Biophysica Acta·Elena GrossiMaite Huarte

❮ Previous
Next ❯

Citations

Sep 8, 2016·Critical Reviews in Biochemistry and Molecular Biology·James A Shapiro
Dec 19, 2016·Wiley Interdisciplinary Reviews. RNA·Ritu Chaudhary, Ashish Lal
May 21, 2020·RNA Biology·Abhinav K Jain
Jul 14, 2020·World Journal of Gastroenterology : WJG·Yue GaoShan Yu
Jan 1, 2020·RNA Biology·Yan HuangXiangting Wang
Mar 25, 2021·Cell Biology International·Surendar AravindhanMajid Ahmadi
Jun 3, 2021·Journal of Personalized Medicine·Jose Carlos BenitezAlfons Navarro

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.