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

Area of Science:

• Molecular Biology
• Cancer Biology
• Genomics

Background:

• Genome-wide studies reveal the tumor suppressor p53 acts as a transcription factor, regulating both gene promoters and enhancers.
• p53 can induce enhancer RNAs and activate distal genes, but its role in regulating long intergenic noncoding RNAs (lincRNAs) and tumor suppression is unclear.

Purpose of the Study:

• To identify and characterize novel p53-regulated lincRNAs involved in tumor suppression.
• To investigate the functional importance of a specific p53-bound lincRNA in p53-mediated cellular responses.

Main Methods:

• Identification and characterization of p53-bound intronic enhancers.
• Analysis of lincRNA expression and its regulation by p53.
• Functional assays to assess the role of lincRNA-475 in cell cycle inhibition and p21/CDKN1A expression.
• Chromatin immunoprecipitation (ChIP) to study p53 and RNA polymerase II binding.

Main Results:

• A novel p53-bound intronic enhancer controlling the lincRNA00475 (linc-475) was identified.
• linc-475 is essential for the p53-dependent induction of cell cycle arrest.
• Loss of linc-475 impairs p53 and RNA polymerase II binding to the p21 promoter, reducing p21/CDKN1A transcription.

Conclusions:

• p53-bound enhancers play a direct role in activating lincRNAs.
• linc-475 is a critical component of the p53 transcriptional response, essential for maintaining p21/CDKN1A levels and tumor suppression.