DNA methyltransferase controls stem cell aging by regulating BMI1 and EZH2 through microRNAs.
Epigenetic regulation of gene expression is well known mechanism that regulates cellular senescence of cancer cells. Here we show that inhibition of DNA methyltransferases (DNMTs) with 5-azacytidine (5-AzaC) or with specific small interfering RNA (siRNA) against DNMT1 and 3b induced the cellular sen...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-05-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3091856?pdf=render |
| _version_ | 1819011137111326720 |
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| author | Ah-Young So Ji-Won Jung Seunghee Lee Hyung-Sik Kim Kyung-Sun Kang |
| author_facet | Ah-Young So Ji-Won Jung Seunghee Lee Hyung-Sik Kim Kyung-Sun Kang |
| author_sort | Ah-Young So |
| collection | DOAJ |
| description | Epigenetic regulation of gene expression is well known mechanism that regulates cellular senescence of cancer cells. Here we show that inhibition of DNA methyltransferases (DNMTs) with 5-azacytidine (5-AzaC) or with specific small interfering RNA (siRNA) against DNMT1 and 3b induced the cellular senescence of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) and increased p16(INK4A) and p21(CIP1/WAF1) expression. DNMT inhibition changed histone marks into the active forms and decreased the methylation of CpG islands in the p16(INK4A) and p21(CIP1/WAF1) promoter regions. Enrichment of EZH2, the key factor that methylates histone H3 lysine 9 and 27 residues, was decreased on the p16(INK4A) and p21(CIP1/WAF1) promoter regions. We found that DNMT inhibition decreased expression levels of Polycomb-group (PcG) proteins and increased expression of microRNAs (miRNAs), which target PcG proteins. Decreased CpG island methylation and increased levels of active histone marks at genomic regions encoding miRNAs were observed after 5-AzaC treatment. Taken together, DNMTs have a critical role in regulating the cellular senescence of hUCB-MSCs through controlling not only the DNA methylation status but also active/inactive histone marks at genomic regions of PcG-targeting miRNAs and p16(INK4A) and p21(CIP1/WAF1) promoter regions. |
| first_indexed | 2024-12-21T01:23:22Z |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T01:23:22Z |
| publishDate | 2011-05-01 |
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| spelling | doaj.art-b06bab6c84f540b9985d2f64486a66872022-12-21T19:20:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-05-0165e1950310.1371/journal.pone.0019503DNA methyltransferase controls stem cell aging by regulating BMI1 and EZH2 through microRNAs.Ah-Young SoJi-Won JungSeunghee LeeHyung-Sik KimKyung-Sun KangEpigenetic regulation of gene expression is well known mechanism that regulates cellular senescence of cancer cells. Here we show that inhibition of DNA methyltransferases (DNMTs) with 5-azacytidine (5-AzaC) or with specific small interfering RNA (siRNA) against DNMT1 and 3b induced the cellular senescence of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) and increased p16(INK4A) and p21(CIP1/WAF1) expression. DNMT inhibition changed histone marks into the active forms and decreased the methylation of CpG islands in the p16(INK4A) and p21(CIP1/WAF1) promoter regions. Enrichment of EZH2, the key factor that methylates histone H3 lysine 9 and 27 residues, was decreased on the p16(INK4A) and p21(CIP1/WAF1) promoter regions. We found that DNMT inhibition decreased expression levels of Polycomb-group (PcG) proteins and increased expression of microRNAs (miRNAs), which target PcG proteins. Decreased CpG island methylation and increased levels of active histone marks at genomic regions encoding miRNAs were observed after 5-AzaC treatment. Taken together, DNMTs have a critical role in regulating the cellular senescence of hUCB-MSCs through controlling not only the DNA methylation status but also active/inactive histone marks at genomic regions of PcG-targeting miRNAs and p16(INK4A) and p21(CIP1/WAF1) promoter regions.http://europepmc.org/articles/PMC3091856?pdf=render |
| spellingShingle | Ah-Young So Ji-Won Jung Seunghee Lee Hyung-Sik Kim Kyung-Sun Kang DNA methyltransferase controls stem cell aging by regulating BMI1 and EZH2 through microRNAs. PLoS ONE |
| title | DNA methyltransferase controls stem cell aging by regulating BMI1 and EZH2 through microRNAs. |
| title_full | DNA methyltransferase controls stem cell aging by regulating BMI1 and EZH2 through microRNAs. |
| title_fullStr | DNA methyltransferase controls stem cell aging by regulating BMI1 and EZH2 through microRNAs. |
| title_full_unstemmed | DNA methyltransferase controls stem cell aging by regulating BMI1 and EZH2 through microRNAs. |
| title_short | DNA methyltransferase controls stem cell aging by regulating BMI1 and EZH2 through microRNAs. |
| title_sort | dna methyltransferase controls stem cell aging by regulating bmi1 and ezh2 through micrornas |
| url | http://europepmc.org/articles/PMC3091856?pdf=render |
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