Epigenetic modifications of SOX2 enhancers, SRR1 and SRR2, correlate with in vitro neural differentiation.
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.
Sikorska
Marianna
M
Neurogenesis and Brain Repair Group, Institute for Biological Sciences, National Research Council Canada, Ottawa, Ontario, Canada. marianna.sikorska@nrc.ca
Sandhu
Jagdeep K
JK
Deb-Rinker
Paromita
P
Jezierski
Anna
A
Leblanc
Julie
J
Charlebois
Claudie
C
Ribecco-Lutkiewicz
Maria
M
Bani-Yaghoub
Mahmud
M
Walker
P Roy
PR
D000107:Acetylation; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D044127:Epigenesis, Genetic / Q000502:physiology*; D024002:HMGB Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*; D018000:Receptors, Peptide / Q000235:genetics / Q000502:physiology*; D055748:SOXB1 Transcription Factors; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D024002:HMGB Proteins; D008562:Membrane Glycoproteins; D018160:Receptors, Cytoplasmic and Nuclear; D018000:Receptors, Peptide; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; C066973:signal sequence receptor