TY - JOUR
T1 - Dimethyl sulfoxide has an impact on epigenetic profile in mouse embryoid body
AU - Iwatani, Misa
AU - Ikegami, Kohta
AU - Kremenska, Yuliya
AU - Hattori, Naka
AU - Tanaka, Satoshi
AU - Yagi, Shintaro
AU - Shiota, Kunio
PY - 2006
Y1 - 2006
N2 - Dimethyl sulfoxide (DMSO), an amphipathic molecule, is widely used not only as a solvent for water-insoluble substances but also as a cryopreservant for various types of cells. Exposure to DMSO sometimes causes unexpected changes in cell fates. Because mammalian development and cellular differentiation are controlled epigenetically by DNA methylation and histone modifications, DMSO likely affects the epigenetic system. The effects of DMSO on transcription of three major DNA methyltransferases (Dnmts) and five well-studied histone modification enzymes were examined in mouse embryonic stem cells and embryoid bodies (EBs) by reverse transcription-polymerase chain reaction. Addition of DMSO (0.02%-1.0%) to EBs in culture induced an increase in Dnmt3a mRNA levels with increasing dosage. Increased expression of two subtypes of Dnmt3a in protein levels was confirmed by Western blotting. Southern blot analysis revealed that DMSO caused hypermethylation of two kinds of repetitive sequences in EBs. Furthermore, restriction landmark genomic scanning, by which DNA methylation status can be analyzed on thousands of loci in genic regions, revealed that DMSO affected DNA methylation status at multiple loci, inducing hypomethylation as well as hypermethylation depending on the genomic loci. In conclusion, DMSO has an impact on the epigenetic profile: upregulation of Dnmt3a expression and alteration of genomewide DNA methylation profiles with phenotypic changes in EBs.
AB - Dimethyl sulfoxide (DMSO), an amphipathic molecule, is widely used not only as a solvent for water-insoluble substances but also as a cryopreservant for various types of cells. Exposure to DMSO sometimes causes unexpected changes in cell fates. Because mammalian development and cellular differentiation are controlled epigenetically by DNA methylation and histone modifications, DMSO likely affects the epigenetic system. The effects of DMSO on transcription of three major DNA methyltransferases (Dnmts) and five well-studied histone modification enzymes were examined in mouse embryonic stem cells and embryoid bodies (EBs) by reverse transcription-polymerase chain reaction. Addition of DMSO (0.02%-1.0%) to EBs in culture induced an increase in Dnmt3a mRNA levels with increasing dosage. Increased expression of two subtypes of Dnmt3a in protein levels was confirmed by Western blotting. Southern blot analysis revealed that DMSO caused hypermethylation of two kinds of repetitive sequences in EBs. Furthermore, restriction landmark genomic scanning, by which DNA methylation status can be analyzed on thousands of loci in genic regions, revealed that DMSO affected DNA methylation status at multiple loci, inducing hypomethylation as well as hypermethylation depending on the genomic loci. In conclusion, DMSO has an impact on the epigenetic profile: upregulation of Dnmt3a expression and alteration of genomewide DNA methylation profiles with phenotypic changes in EBs.
KW - Differentiation
KW - Dimethyl sulfoxide
KW - DNA methylation
KW - DNA methyltransferase
KW - Epigenetics
UR - http://www.scopus.com/inward/record.url?scp=33750565544&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33750565544&partnerID=8YFLogxK
U2 - 10.1634/stemcells.2005-0427
DO - 10.1634/stemcells.2005-0427
M3 - Article
C2 - 16840553
AN - SCOPUS:33750565544
SN - 1066-5099
VL - 24
SP - 2549
EP - 2556
JO - Stem Cells
JF - Stem Cells
IS - 11
ER -