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

Abigail F Groff1, Diana B Sanchez-Gomez2, Marcela M L Soruco3

  • 1Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Cell Reports
|August 16, 2016
PubMed

Insights

The Linc-p21 locus

Area of Science:

  • Molecular Biology
  • Genomics
  • Epigenetics

Background:

  • The Linc-p21 locus encodes a long non-coding RNA crucial for p53 signaling, cell-cycle regulation, and tumor suppression.
  • Its precise mechanism of action, whether RNA-dependent or independent, remains debated.

Purpose of the Study:

  • To elucidate the functional elements and regulatory mechanisms of the Linc-p21 locus.
  • To differentiate between RNA-mediated and DNA-mediated regulatory effects.

Main Methods:

  • Utilized a knockout mouse model to assess Linc-p21 locus function.
  • Employed a massively parallel enhancer assay for nucleotide-resolution interrogation of DNA sequences.
  • Analyzed gene expression changes, including the cell-cycle regulator Cdkn1a, upon locus deletion.

Main Results:

  • Deletion of the Linc-p21 locus impacted local gene expression, even in tissues lacking detectable Linc-p21 transcripts.
  • Identified multiple functional DNA enhancer elements within the Linc-p21 locus.
  • Demonstrated RNA-independent regulatory effects mediated by DNA elements.

Conclusions:

  • The cis-regulatory effects of the Linc-p21 locus in vivo are primarily mediated by DNA enhancer elements.
  • These enhancer elements exert regulatory control irrespective of Linc-p21 transcript presence or absence.
  • Findings clarify the locus's mechanism of action, highlighting the role of cis-regulatory DNA elements.

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