title: Unlinking an lncRNA from Its Associated cis Element.
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.
authors.affiliation: Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: vikram.paralkar@uphs.upenn.edu.
authors.forename: Vikram R
authors.initials: VR
authors.lastname: Paralkar
authors.affiliation: Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Cristian C
authors.initials: CC
authors.lastname: Taborda
authors.affiliation: Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Center for Systems and Computational Biology, The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Kossenkov
authors.affiliation: Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Rishi
authors.initials: R
authors.lastname: Prasad
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Luan
authors.affiliation: Medical Research Council, Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford OX3 9DS, UK.
authors.forename: James O J
authors.initials: JO
authors.lastname: Davies
authors.affiliation: Medical Research Council, Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford OX3 9DS, UK.
authors.forename: Jim R
authors.initials: JR
authors.lastname: Hughes
authors.affiliation: 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.
authors.forename: Ross C
authors.initials: RC
authors.lastname: Hardison
authors.affiliation: Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Gerd A
authors.initials: GA
authors.lastname: Blobel
authors.affiliation: Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: mitch.weiss@stjude.org.
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Weiss
mesh_terms: D000818:Animals; D002460:Cell Line; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D051379:Mice; D011061:Poly A / Q000378:metabolism; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: C493961:Cdkn1b protein, mouse; C000610305:Lockd long noncoding RNA, mouse; D062085:RNA, Long Noncoding; D050760:Cyclin-Dependent Kinase Inhibitor p27; D011061:Poly A