Abstract
DNAmethylation is an epigenetic mechanism regulating gene expression. In this study, we observed that DNAmethyltransferase 3a (Dnmt3a) expression is decreased after muscle atrophy.Wemade skeletalmuscle-specific Dnmt3a-knockout (Dnmt3a-KO) mice. The regeneration capacity after muscle injury was markedly decreased in Dnmt3a-KOmice.DiminishedmRNAand protein expression of Dnmt3awere observed in skeletalmuscles aswell as in satellite cells, which are important formuscle regeneration, in Dnmt3a-KOmice. Dnmt3a-KO satellite cell showed smaller in size (length/area), suggesting suppressed myotube differentiation. Microarray analysis of satellite cells showed that expression of growth differentiation factor 5 (Gdf5)mRNAwasmarkedly increased in Dnmt3a-KOmice. TheDNA methylation level of the Gdf5 promoter wasmarkedly decreased in Dnmt3a-KO satellite cells. In addition, DNA methylation inhibitor azacytidine treatment increased Gdf5 expression in wild-type satellite cells, suggesting Gdf5 expression is regulated byDNAmethylation. Also, we observed increased inhibitor of differentiation (a target of Gdf5)mRNA expression in Dnmt3a-KO satellite cells. Thus, Dnmt3a appears to regulate satellite cell differentiation viaDNAmethylation. Thismechanism may play a role in the decreased regeneration capacity during atrophy such as in aged sarcopenia.
| Original language | English |
|---|---|
| Pages (from-to) | 1452-1467 |
| Number of pages | 16 |
| Journal | FASEB Journal |
| Volume | 32 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2018 |
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All Science Journal Classification (ASJC) codes
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics
Cite this
Reduced Dnmt3a increases Gdf5 expression with suppressed satellite cell differentiation and impaired skeletal muscle regeneration. / Hatazawa, Yukino; Ono, Yusuke; Hirose, Yuma; Kanai, Sayaka; Fujii, Nobuharu L.; Machida, Shuichi; Nishino, Ichizo; Shimizu, Takahiko; Okano, Masaki; Kamei, Yasutomi; Ogawa, Yoshihiro.
In: FASEB Journal, Vol. 32, No. 3, 03.2018, p. 1452-1467.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Reduced Dnmt3a increases Gdf5 expression with suppressed satellite cell differentiation and impaired skeletal muscle regeneration
AU - Hatazawa, Yukino
AU - Ono, Yusuke
AU - Hirose, Yuma
AU - Kanai, Sayaka
AU - Fujii, Nobuharu L.
AU - Machida, Shuichi
AU - Nishino, Ichizo
AU - Shimizu, Takahiko
AU - Okano, Masaki
AU - Kamei, Yasutomi
AU - Ogawa, Yoshihiro
PY - 2018/3
Y1 - 2018/3
N2 - DNAmethylation is an epigenetic mechanism regulating gene expression. In this study, we observed that DNAmethyltransferase 3a (Dnmt3a) expression is decreased after muscle atrophy.Wemade skeletalmuscle-specific Dnmt3a-knockout (Dnmt3a-KO) mice. The regeneration capacity after muscle injury was markedly decreased in Dnmt3a-KOmice.DiminishedmRNAand protein expression of Dnmt3awere observed in skeletalmuscles aswell as in satellite cells, which are important formuscle regeneration, in Dnmt3a-KOmice. Dnmt3a-KO satellite cell showed smaller in size (length/area), suggesting suppressed myotube differentiation. Microarray analysis of satellite cells showed that expression of growth differentiation factor 5 (Gdf5)mRNAwasmarkedly increased in Dnmt3a-KOmice. TheDNA methylation level of the Gdf5 promoter wasmarkedly decreased in Dnmt3a-KO satellite cells. In addition, DNA methylation inhibitor azacytidine treatment increased Gdf5 expression in wild-type satellite cells, suggesting Gdf5 expression is regulated byDNAmethylation. Also, we observed increased inhibitor of differentiation (a target of Gdf5)mRNA expression in Dnmt3a-KO satellite cells. Thus, Dnmt3a appears to regulate satellite cell differentiation viaDNAmethylation. Thismechanism may play a role in the decreased regeneration capacity during atrophy such as in aged sarcopenia.
AB - DNAmethylation is an epigenetic mechanism regulating gene expression. In this study, we observed that DNAmethyltransferase 3a (Dnmt3a) expression is decreased after muscle atrophy.Wemade skeletalmuscle-specific Dnmt3a-knockout (Dnmt3a-KO) mice. The regeneration capacity after muscle injury was markedly decreased in Dnmt3a-KOmice.DiminishedmRNAand protein expression of Dnmt3awere observed in skeletalmuscles aswell as in satellite cells, which are important formuscle regeneration, in Dnmt3a-KOmice. Dnmt3a-KO satellite cell showed smaller in size (length/area), suggesting suppressed myotube differentiation. Microarray analysis of satellite cells showed that expression of growth differentiation factor 5 (Gdf5)mRNAwasmarkedly increased in Dnmt3a-KOmice. TheDNA methylation level of the Gdf5 promoter wasmarkedly decreased in Dnmt3a-KO satellite cells. In addition, DNA methylation inhibitor azacytidine treatment increased Gdf5 expression in wild-type satellite cells, suggesting Gdf5 expression is regulated byDNAmethylation. Also, we observed increased inhibitor of differentiation (a target of Gdf5)mRNA expression in Dnmt3a-KO satellite cells. Thus, Dnmt3a appears to regulate satellite cell differentiation viaDNAmethylation. Thismechanism may play a role in the decreased regeneration capacity during atrophy such as in aged sarcopenia.
UR - http://www.scopus.com/inward/record.url?scp=85043594065&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85043594065&partnerID=8YFLogxK
U2 - 10.1096/fj.201700573R
DO - 10.1096/fj.201700573R
M3 - Article
C2 - 29146735
AN - SCOPUS:85043594065
VL - 32
SP - 1452
EP - 1467
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 3
ER -