Cited by 209Developmental Biology and Gene RegulationCancer-related molecular mechanisms researchGenomics and Chromatin Dynamics

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

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Amaral, Paulo P., Neyt, Christine, Wilkins, Simon J., Askarian-Amiri, Marjan E., Sunkin, Susan M., Perkins, Andrew C., Mattick, John S.·2009·RNA

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.

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Crossref · 10.1261/rna.1705309

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  • SOX2-OT is a heavily spliced, evolutionarily conserved lncRNA with predominant brain expression and is a hub of these oligodendrocyte modules.

    “SOX2-OT is a heavily spliced, evolutionarily-conserved lncRNA exhibiting predominant brain expression and a hub of these oligodendrocyte modules, without previous mechanistic links to myelination (75, 76).”

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Authors
Amaral, P. P., Neyt, C., Wilkins, S. J., Askarian-Amiri, M. E., Sunkin, S. M., Perkins, A. C., & Mattick, J. S.
Affiliations
  • The University of Queensland (AU)
  • Allen Institute for Brain Science (US)
Venue
RNA
Published
2009-09-18
Volume
15
Issue
11
Pages
2013-2027
ISSN
  • 1355-8382 (ISSN-L)
  • 1469-9001
OpenAlex
W2163141464
Cited by
209
References
109
Citations by year
2026: 3 · 2025: 4 · 2024: 5 · 2023: 18 · 2022: 9 · 2021: 16 · 2020: 18 · 2019: 13 · 2018: 19 · 2017: 22 · 2016: 15 · 2015: 12 · 2014: 13 · 2013: 17 · 2012: 10
FWCI
3.36
Type
journal article
Language
en
Open access
Locations
  • RNA (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • ResearchSpace (University of Auckland) (submittedVersion)
Funders
  • University of Queensland
  • Australian Research Council (FF0561986)
  • National Health and Medical Research Council (455871)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • 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
Keywords
SOX2OT, SOX2, long non-coding RNA, transcription start sites, gene expression regulation, pluripotency, embryoid body differentiation, mesoderm differentiation, mouse embryonic stem cells, adult neurogenesis, brain, vertebrate embryonic development, central nervous system, chickens, zebrafish
MeSH terms
Amino Acid Sequence, Animals, Cell Differentiation, Cell Line, Embryo, Mammalian, Genes, Overlapping, Humans, Neurons, Organ Specificity, Transcription, Genetic, Zebrafish, Gene Expression Regulation, Developmental, Cell Lineage, Zebrafish Proteins, Mice, SOX Transcription Factors, SOXB1 Transcription Factors

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