Epigenetic modifications of SOX2 enhancers, SRR1 and SRR2, correlate with in vitro neural differentiation: J.Neurosci.Res.

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TypeArticle
Journal titleJ Neurosci Res.
Volume86
Issue8
Pages16801693; # of pages: 14
SubjectAcetylation; Astrocytes; Base Sequence; biosynthesis; Brain; Calcium-Binding Proteins; Canada; cell; Cell Differentiation; CELLS; Cells,Cultured; Comparative Study; cytology; DNA; DNA Methylation; DNA-Binding Proteins; Enhancer Elements,Genetic; Epigenesis,Genetic; EXPRESSION; GENE; genetics; glycoprotein; Glycoproteins; HMGB Proteins; Human; Humans; In Vitro; MECHANISMS; membrane; Membrane Glycoproteins; metabolism; Methylation; MOLECULAR; Molecular Sequence Data; Neurogenesis; Neurons; NUCLEAR; peptide; physiology; protein; Proteins; receptor; Receptors,Cytoplasmic and Nuclear; Receptors,Peptide; Role; SEQUENCE; SOXB1 Transcription Factors; Stem Cells; Transcription Factors
AbstractSOX2 is a key neurodevelopmental gene involved in maintaining the pluripotency of stem cells and proliferation of neural progenitors and astroglia. Two evolutionally conserved enhancers, SRR1 and SRR2, are involved in controlling SOX2 expression during neurodevelopment; however, the molecular mechanisms regulating their activity are not known. We have examined DNA methylation and histone H3 acetylation at both enhancers in NT2-D1 progenitors, neurons and astrocytes, to establish the role of epigenetic mechanisms in cell-type-specific SOX2 expression. This study showed that 1) unmethylated DNA and acetylated histones at both enhancers correlated with a high level of SOX2 expression in proliferating neural progenitors and 2) reversible modifications of the SRR1 element were observed during gene reexpression in astrocytes, whereas permanent epigenetic marks on the SRR2 enhancer were seen in neurons where the gene was silenced. Taken together, these results are clear illustrations of cell-type-specific epigenomes and suggest mechanisms by which they may be created and maintained
Publication date
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedNo
NRC numberSIKORSKA2008
NPARC number9367961
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Record identifierb609dee8-616d-459c-b341-94f61065b375
Record created2009-07-10
Record modified2016-05-09
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