Format

Send to

Choose Destination
See comment in PubMed Commons below
Mol Cell. 2016 Apr 7;62(1):104-10. doi: 10.1016/j.molcel.2016.02.029. Epub 2016 Mar 31.

Unlinking an lncRNA from Its Associated cis Element.

Author information

1
Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: vikram.paralkar@uphs.upenn.edu.
2
Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
3
Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
4
Center for Systems and Computational Biology, The Wistar Institute, Philadelphia, PA 19104, USA.
5
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
6
Medical Research Council, Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford OX3 9DS, UK.
7
Center for Comparative Genomics and Bioinformatics, Pennsylvania State University, University Park, PA 16801, USA; Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16801, USA.
8
Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: mitch.weiss@stjude.org.

Abstract

Long non-coding (lnc) RNAs can regulate gene expression and protein functions. However, the proportion of lncRNAs with biological activities among the thousands expressed in mammalian cells is controversial. We studied Lockd (lncRNA downstream of Cdkn1b), a 434-nt polyadenylated lncRNA originating 4 kb 3' to the Cdkn1b gene. Deletion of the 25-kb Lockd locus reduced Cdkn1b transcription by approximately 70% in an erythroid cell line. In contrast, homozygous insertion of a polyadenylation cassette 80 bp downstream of the Lockd transcription start site reduced the entire lncRNA transcript level by >90% with no effect on Cdkn1b transcription. The Lockd promoter contains a DNase-hypersensitive site, binds numerous transcription factors, and physically associates with the Cdkn1b promoter in chromosomal conformation capture studies. Therefore, the Lockd gene positively regulates Cdkn1b transcription through an enhancer-like cis element, whereas the lncRNA itself is dispensable, which may be the case for other lncRNAs.

PMID:
27041223
PMCID:
PMC4877494
[Available on 2017-04-07]
DOI:
10.1016/j.molcel.2016.02.029
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center