Complex architecture and regulated expression of the Sox2ot locus during vertebrate development

Amaral, Paulo P., Neyt, Christine, Wilkins, Simon J., Askarian-Amiri, Marjan E., Sunkin, Susan M., Perkins, Andrew C. and Mattick, John S. (2009) Complex architecture and regulated expression of the Sox2ot locus during vertebrate development. RNA, 15 11: 2013-2027. doi:10.1261/rna.1705309

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Author Amaral, Paulo P.
Neyt, Christine
Wilkins, Simon J.
Askarian-Amiri, Marjan E.
Sunkin, Susan M.
Perkins, Andrew C.
Mattick, John S.
Title Complex architecture and regulated expression of the Sox2ot locus during vertebrate development
Journal name RNA   Check publisher's open access policy
ISSN 1355-8382
Publication date 2009-11
Year available 2009
Sub-type Article (original research)
DOI 10.1261/rna.1705309
Open Access Status File (Publisher version)
Volume 15
Issue 11
Start page 2013
End page 2027
Total pages 15
Editor T. W. Nilsen
Place of publication Woodbury, NY, United States
Publisher Cold Spring Harbor Laboratory Press
Collection year 2010
Language eng
Formatted abstract
 The Sox2 gene is a key regulator of pluripotency embedded within an intron of a long noncoding RNA (ncRNA), termed Sox2 overlapping transcript (Sox2ot), which is transcribed in the same orientation. However, this ncRNA remains uncharacterized. Here we show that Sox2ot has multiple transcription start sites associated with genomic features that indicate regulated expression, including highly conserved elements (HCEs) and chromatin marks characteristic of gene promoters. To identify biological processes in which Sox2ot may be involved, we analyzed its expression in several developmental systems, compared to expression of Sox2. We show that Sox2ot is a stable transcript expressed in mouse embryonic stem cells, which, like Sox2, is down-regulated upon induction of embryoid body (EB) differentiation. However, in contrast to Sox2, Sox2ot is up-regulated during EB mesoderm-lineage differentiation. In adult mouse, Sox2ot isoforms were detected in tissues where Sox2 is expressed, as well as in different tissues, supporting independent regulation of expression of the ncRNA. Sox2dot, an isoform of Sox2ot transcribed from a distal HCE located >500 kb upstream of Sox2, was detected exclusively in the mouse brain, with enrichment in regions of adult neurogenesis. In addition, Sox2ot isoforms are transcribed from HCEs upstream of Sox2 in other vertebrates, including in several regions of the human brain. We also show that Sox2ot is dynamically regulated during chicken and zebrafish embryogenesis, consistently associated with central nervous system structures. These observations provide insight into the structure and regulation of the Sox2ot gene, and suggest conserved roles for Sox2ot orthologs during vertebrate development.                   
Keyword noncoding RNA
embryonic stem cells
central nervous system
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 63 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 67 times in Scopus Article | Citations
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Created: Mon, 23 Nov 2009, 15:26:02 EST