Long Noncoding RNAs with Enhancer-like Function in Human Cells
Open accessAbstract
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.
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Wide-ranging alterations in abundance of enhancer RNAs at sites coinciding with cCRE were uncovered.
“we uncovered wide-ranging alterations in the abundance of enhancer RNAs, a hallmark of active enhancers (40), at sites coinciding with cCRE.”
From PU.1-Dependent Enhancer Inhibition Separates <i>Tet2</i> -Deficient Hematopoiesis from Malignant Transformation (2022) · cites this paper as [40]
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“In support, we uncovered wideranging alterations in the abundance of enhancer RNAs, a hallmark of active enhancers (40), at sites coinciding with cCRE.”
BackgroundGenetic variation within transcriptional regulatory elements and its implications for human disease
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- Authors
- Ørom, U. A., Derrien, T., Beringer, M., Gumireddy, K., Gardini, A., Bussotti, G., Lai, F., Zytnicki, M., Notredame, C., Huang, Q., Guigo, R., & Shiekhattar, R.
- Affiliations
- The Wistar Institute (US)
- Centre for Genomic Regulation (ES)
- Corresponding author
- Shiekhattar, Ramin
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 143
- Issue
- 1
- Pages
- 46-58
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4108080
- OpenAlex
- W2134033103
- Cited by
- 1,721
- References
- 7
- Citations by year
- 2026: 22 · 2025: 27 · 2024: 43 · 2023: 47 · 2022: 58 · 2021: 119 · 2020: 105 · 2019: 131 · 2018: 151 · 2017: 148 · 2016: 171 · 2015: 162 · 2014: 178 · 2013: 151 · 2012: 113
- FWCI
- 33.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1020 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, other-oa)
- Funders
- National Institutes of Health (5u54hg004555-04)
- National Human Genome Research Institute (U54 HG004555-01)
- National Cancer Institute (P30CA010815)
- National Institute of General Medical Sciences (GM-079091, R01GM079091)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- long non-coding RNA, gene activation, SCL/TAL1, SNAI1, SNAI2, hematopoiesis, developmental regulators, human cell lines, transcriptional regulation
- MeSH terms
- Snail Family Transcription Factors, Cell Line, Cells, Cultured, Enhancer Elements, Genetic, Humans, RNA, Messenger, Transcription Factors, Transcriptional Activation, Genome, Human, RNA, Untranslated, Cell Line, Tumor
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