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In Vivo Characterization of Linc-p21 Reveals Functional cis-Regulatory DNA Elements.
Groff, Abigail F; Sanchez-Gomez, Diana B; Soruco, Marcela M L; Gerhardinger, Chiara; Barutcu, A Rasim; Li, Eric; Elcavage, Lara; Plana, Olivia; Sanchez, Lluvia V; Lee, James C; Sauvageau, Martin; Rinn, John L.
Afiliación
  • Groff AF; Department 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.
  • Sanchez-Gomez DB; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Soruco MML; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
  • Gerhardinger C; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Barutcu AR; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Li E; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Elcavage L; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Plana O; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Sanchez LV; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Lee JC; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Sauvageau M; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
  • Rinn JL; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. Electronic address: john_rinn@harvard.edu.
Cell Rep ; 16(8): 2178-2186, 2016 08 23.
Article en En | MEDLINE | ID: mdl-27524623
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Secuencia de Bases / Proteína p53 Supresora de Tumor / Elementos de Facilitación Genéticos / Eliminación de Secuencia / Inhibidor p21 de las Quinasas Dependientes de la Ciclina / ARN Largo no Codificante Límite: Animals Idioma: En Revista: Cell Rep Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Secuencia de Bases / Proteína p53 Supresora de Tumor / Elementos de Facilitación Genéticos / Eliminación de Secuencia / Inhibidor p21 de las Quinasas Dependientes de la Ciclina / ARN Largo no Codificante Límite: Animals Idioma: En Revista: Cell Rep Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos