Conserved long noncoding RNAs transcriptionally regulated by Oct4 and Nanog modulate pluripotency in mouse embryonic stem cells
(2010) In RNA 16(2). p.324-337- Abstract
- The genetic networks controlling stem cell identity are the focus of intense interest, due to their obvious therapeutic potential as well as exceptional relevance to models of early development. Genome-wide mapping of transcriptional networks in mouse embryonic stem cells (mESCs) reveals that many endogenous noncoding RNA molecules, including long noncoding RNAs (lncRNAs), may play a role in controlling the pluripotent state. We performed a genome-wide screen that combined full-length mESC transcriptome genomic mapping data with chromatin immunoprecipitation genomic location maps of the key mESC transcription factors Oct4 and Nanog. We henceforth identified four mESC-expressed, conserved lncRNA-encoding genes residing proximally to active... (More)
- The genetic networks controlling stem cell identity are the focus of intense interest, due to their obvious therapeutic potential as well as exceptional relevance to models of early development. Genome-wide mapping of transcriptional networks in mouse embryonic stem cells (mESCs) reveals that many endogenous noncoding RNA molecules, including long noncoding RNAs (lncRNAs), may play a role in controlling the pluripotent state. We performed a genome-wide screen that combined full-length mESC transcriptome genomic mapping data with chromatin immunoprecipitation genomic location maps of the key mESC transcription factors Oct4 and Nanog. We henceforth identified four mESC-expressed, conserved lncRNA-encoding genes residing proximally to active genomic binding sites of Oct4 and Nanog. Accordingly, these four genes have potential roles in pluripotency. We show that two of these lncRNAs, AK028326 (Oct4-activated) and AK141205 (Nanog-repressed), are direct targets of Oct4 and Nanog. Most importantly, we demonstrate that these lncRNAs are not merely controlled by mESC transcription factors, but that they themselves regulate developmental state: knockdown and overexpression of these transcripts lead to robust changes in Oct4 and Nanog mRNA levels, in addition to alterations in cellular lineage-specific gene expression and in the pluripotency of mESCs. We further characterize AK028326 as a co-activator of Oct4 in a regulatory feedback loop. These results for the first time implicate lncRNAs in the modulation of mESC pluripotency and expand the established mESC regulatory network model to include functional lncRNAs directly controlled by key mESC transcription factors. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1547164
- author
- Mohamed, Jameelah Sheik ; Gaughwin, Philip LU ; Lim, Bing ; Robson, Paul and Lipovich, Leonard
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Gomafu, differentiation, ncRNA, mouse embryonic stem cells/mESCs, RNCR2, C18ORF22
- in
- RNA
- volume
- 16
- issue
- 2
- pages
- 324 - 337
- publisher
- Cold Spring Harbor Laboratory Press (CSHL)
- external identifiers
-
- wos:000273868900010
- scopus:75149163987
- pmid:20026622
- ISSN
- 1355-8382
- DOI
- 10.1261/rna.1441510
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neuronal Survival (013212041)
- id
- 2dc78e56-0d9d-41ea-b03b-189a57d64f4a (old id 1547164)
- date added to LUP
- 2016-04-01 13:07:56
- date last changed
- 2022-04-21 19:56:33
@article{2dc78e56-0d9d-41ea-b03b-189a57d64f4a,
abstract = {{The genetic networks controlling stem cell identity are the focus of intense interest, due to their obvious therapeutic potential as well as exceptional relevance to models of early development. Genome-wide mapping of transcriptional networks in mouse embryonic stem cells (mESCs) reveals that many endogenous noncoding RNA molecules, including long noncoding RNAs (lncRNAs), may play a role in controlling the pluripotent state. We performed a genome-wide screen that combined full-length mESC transcriptome genomic mapping data with chromatin immunoprecipitation genomic location maps of the key mESC transcription factors Oct4 and Nanog. We henceforth identified four mESC-expressed, conserved lncRNA-encoding genes residing proximally to active genomic binding sites of Oct4 and Nanog. Accordingly, these four genes have potential roles in pluripotency. We show that two of these lncRNAs, AK028326 (Oct4-activated) and AK141205 (Nanog-repressed), are direct targets of Oct4 and Nanog. Most importantly, we demonstrate that these lncRNAs are not merely controlled by mESC transcription factors, but that they themselves regulate developmental state: knockdown and overexpression of these transcripts lead to robust changes in Oct4 and Nanog mRNA levels, in addition to alterations in cellular lineage-specific gene expression and in the pluripotency of mESCs. We further characterize AK028326 as a co-activator of Oct4 in a regulatory feedback loop. These results for the first time implicate lncRNAs in the modulation of mESC pluripotency and expand the established mESC regulatory network model to include functional lncRNAs directly controlled by key mESC transcription factors.}},
author = {{Mohamed, Jameelah Sheik and Gaughwin, Philip and Lim, Bing and Robson, Paul and Lipovich, Leonard}},
issn = {{1355-8382}},
keywords = {{Gomafu; differentiation; ncRNA; mouse embryonic stem cells/mESCs; RNCR2; C18ORF22}},
language = {{eng}},
number = {{2}},
pages = {{324--337}},
publisher = {{Cold Spring Harbor Laboratory Press (CSHL)}},
series = {{RNA}},
title = {{Conserved long noncoding RNAs transcriptionally regulated by Oct4 and Nanog modulate pluripotency in mouse embryonic stem cells}},
url = {{http://dx.doi.org/10.1261/rna.1441510}},
doi = {{10.1261/rna.1441510}},
volume = {{16}},
year = {{2010}},
}