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Epigenetic modifications of SOX2 enhancers, SRR1 and SRR2, correlate with in vitro neural differentiation
Author(s) -
Sikorska Marianna,
Sandhu Jagdeep K.,
DebRinker Paromita,
Jezierski Anna,
LeBlanc Julie,
Charlebois Claudie,
RibeccoLutkiewicz Maria,
BaniYaghoub Mahmud,
Walker P. Roy
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21635
Subject(s) - sox2 , epigenetics , enhancer , biology , dna methylation , epigenetic regulation of neurogenesis , histone , progenitor cell , microbiology and biotechnology , neural stem cell , epigenomics , cellular differentiation , acetylation , regulation of gene expression , gene expression , genetics , stem cell , gene , embryonic stem cell
SOX2 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. © 2008 Wiley‐Liss, Inc.