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PMID: 20887892 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Long noncoding RNAs with enhancer-like function in human cells.

Cell ·Vol. 143 ·No. 1 ·2010-10-01 ·Pages 46-58

Ørom UA, Derrien T, Beringer M, Gumireddy K, Gardini A, Bussotti G, Lai F, Zytnicki M, Notredame C, Huang Q, Guigo R, Shiekhattar R

Abstract

While the long noncoding RNAs (ncRNAs) constitute a large portion of the mammalian transcriptome, their biological functions has remained elusive. A few long ncRNAs that have been studied in any detail silence gene expression in processes such as X-inactivation and imprinting. We used a GENCODE annotation of the human genome to characterize over a thousand long ncRNAs that are expressed in multiple cell lines. Unexpectedly, we found an enhancer-like function for a set of these long ncRNAs in human cell lines. Depletion of a number of ncRNAs led to decreased expression of their neighboring protein-coding genes, including the master regulator of hematopoiesis, SCL (also called TAL1), Snai1 and Snai2. Using heterologous transcription assays we demonstrated a requirement for the ncRNAs in activation of gene expression. These results reveal an unanticipated role for a class of long ncRNAs in activation of critical regulators of development and differentiation.

MeSH Terms
Cell Line Cell Line, Tumor Cells, Cultured Enhancer Elements, Genetic Genome, Human Humans RNA, Messenger/genetics RNA, Untranslated/metabolism Snail Family Transcription Factors Transcription Factors/genetics Transcriptional Activation
Chemicals
RNA, Messenger RNA, Untranslated SNAI1 protein, human SNAI2 protein, human Snail Family Transcription Factors Transcription Factors
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Ørom Ulf Andersson
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Derrien Thomas
Beringer Malte
Gumireddy Kiranmai
Gardini Alessandro
Bussotti Giovanni
Lai Fan
Zytnicki Matthias
Notredame Cedric
Huang Qihong
Guigo Roderic
Shiekhattar Ramin
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
Published
2010-10-01
Pages
46-58
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC4108080
Subset
IM
Grants
NIGMS NIH HHS · R01 GM079091 · United States
NIGMS NIH HHS · R01 GM079091-03 · United States
NCI NIH HHS · P30 CA010815 · United States
NIGMS NIH HHS · R01 GM079091-04 · United States
NIGMS NIH HHS · GM 079091 · United States
NHGRI NIH HHS · U54 HG004555-01 · United States
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