@article{e3e8b735bd194a7ba57642afb50cb5a5,
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.",
author = "Paralkar, {Vikram R.} and Taborda, {Cristian C.} and Peng Huang and Yu Yao and Kossenkov, {Andrew V.} and Rishi Prasad and Jing Luan and Davies, {James O.J.} and Hughes, {Jim R.} and Hardison, {Ross C.} and Blobel, {Gerd A.} and Weiss, {Mitchell J.}",
note = "Funding Information: We thank Peter Klein, Feng Zhang, and Kosuke Yusa for providing us with CRISPR-Cas9 plasmids. We thank Chuck Sherr and Chunliang Lee for helpful discussions. This work was supported by an ASH Scholar Award (to V.R.P.), a University of Pennsylvania Measey Fellowship Award (to V.R.P.), an NIDDK T32 training grant (to V.R.P.), NIDDK K08 1K08DK102533-01A1 award (to V.R.P.), NIDDK R01 DK092318 award (to M.J.W.), NHLBI RO1HL119479 award (to G.A.B.), NIDDK R56 DK065806 award (to R.C.H.), Wellcome Trust Clinical Research Training Fellowship 098931/Z/12/Z (to J.O.J.D.), Wellcome Trust Strategic Award 106130/Z/14/Z (to J.R.H.), and Medical Research Council Core Funding and Centenary Award 4050189188) (to J.R.H.). Funding Information: We thank Peter Klein, Feng Zhang, and Kosuke Yusa for providing us with CRISPR-Cas9 plasmids. We thank Chuck Sherr and Chunliang Lee for helpful discussions. This work was supported by an ASH Scholar Award (to V.R.P.), a University of Pennsylvania Measey Fellowship Award (to V.R.P.), an NIDDK T32 training grant (to V.R.P.), NIDDK K08 1K08DK102533-01A1 award (to V.R.P.), NIDDK R01 DK092318 award (to M.J.W.), NIDDK R56 DK065806 award (to R.C.H.), Wellcome Trust Clinical Research Training Fellowship 098931/Z/12/Z (to J.O.J.D.), Wellcome Trust Strategic Award 106130/Z/14/Z (to J.R.H.), and Medical Research Council Core Funding and Centenary Award 4050189188) (to J.R.H.). Publisher Copyright: {\textcopyright} 2016 Elsevier Inc..",
year = "2016",
month = apr,
day = "7",
doi = "10.1016/j.molcel.2016.02.029",
language = "English (US)",
volume = "62",
pages = "104--110",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "1",
}