In Vivo Characterization of Linc-p21 Reveals Functional cis-Regulatory DNA Elements.

Cell Rep
Authors
Abstract

The Linc-p21 locus, encoding a long non-coding RNA, plays an important role in p53 signaling, cell-cycle regulation, and tumor suppression. However, despite extensive study, confusion exists regarding its mechanism of action: is activity driven by the transcript acting in trans, in cis, or by an underlying functional enhancer? Here, using a knockout mouse model and a massively parallel enhancer assay, we delineate the functional elements at this locus. We observe that, even in tissues with no detectable Linc-p21 transcript, deletion of the locus significantly affects local gene expression, including of the cell-cycle regulator Cdkn1a. To characterize this RNA-independent regulatory effect, we systematically interrogated the underlying DNA sequence for enhancer activity at nucleotide resolution and confirmed the existence of multiple enhancer elements. Together, these data suggest that, in vivo, the cis-regulatory effects mediated by Linc-p21, in the presence or absence of transcription, are due to DNA enhancer elements.

Year of Publication
2016
Journal
Cell Rep
Volume
16
Issue
8
Pages
2178-86
Date Published
2016 Aug 23
ISSN
2211-1247
DOI
10.1016/j.celrep.2016.07.050
PubMed ID
27524623
PubMed Central ID
PMC5014909
Links
Grant list
P01 GM099117 / GM / NIGMS NIH HHS / United States
R01 MH102416 / MH / NIMH NIH HHS / United States