PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells
DNMT3L, a member of DNA methyltransferases family, is present only in mammals. As it provides specificity to the action of de novo methyltransferases, DNMT3A and DNMT3B and interacts with histone H3, DNMT3L has been invoked as the molecule that can read the histone code and translate it into DNA met...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/100783 |
| _version_ | 1826212589828308992 |
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| author | Das, Partha Pratim Hendrix, David A. Apostolou, Effie Buchner, Alice H. Canver, Matthew C. Beyaz, Semir Ljuboja, Damir Kuintzle, Rachael Kim, Woojin Karnik, Rahul Shao, Zhen Xie, Huafeng Xu, Jian De Los Angeles, Alejandro Zhang, Yingying Choe, Junho Jun, Don Leong Jia Shen, Xiaohua Gregory, Richard I. Daley, George Q. Meissner, Alexander Kellis, Manolis Hochedlinger, Konrad Kim, Jonghwan Orkin, Stuart H. Hendrix, David A. |
| author2 | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory |
| author_facet | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Das, Partha Pratim Hendrix, David A. Apostolou, Effie Buchner, Alice H. Canver, Matthew C. Beyaz, Semir Ljuboja, Damir Kuintzle, Rachael Kim, Woojin Karnik, Rahul Shao, Zhen Xie, Huafeng Xu, Jian De Los Angeles, Alejandro Zhang, Yingying Choe, Junho Jun, Don Leong Jia Shen, Xiaohua Gregory, Richard I. Daley, George Q. Meissner, Alexander Kellis, Manolis Hochedlinger, Konrad Kim, Jonghwan Orkin, Stuart H. Hendrix, David A. |
| author_sort | Das, Partha Pratim |
| collection | MIT |
| description | DNMT3L, a member of DNA methyltransferases family, is present only in mammals. As it provides specificity to the action of de novo methyltransferases, DNMT3A and DNMT3B and interacts with histone H3, DNMT3L has been invoked as the molecule that can read the histone code and translate it into DNA methylation. It plays an important role in the initiation of genomic imprints during gametogenesis and in nuclear reprogramming. With important functions attributed to it, it is imperative that the DNMT3L expression is tightly controlled. Previously, we had identified a CpG island within the human DNMT3L promoter and first exon that showed loss of DNA methylation in cancer samples. Here we show that this Differentially Methylated CpG island within DNMT3L (DNMT3L DMC) acts to repress transcription, is a Polycomb/Trithorax Response Element (PRE) and interacts with both PRC1 and PRC2 Polycomb repressive complexes. In addition, it adopts inactive chromatin conformation and is associated with other inactive chromatin-specific proteins like SUV39H1 and HP1. The presence of DNMT3L DMC also influences the adjacent promoter to adopt repressive histone post-translational modifications. Due to its association with multiple layers of repressive epigenetic modifications, we believe that PRE within the DNMT3L DMC is responsible for the tight regulation of DNMT3L expression and the aberrant epigenetic modifications of this region leading to DNMT3L overexpression could be the reason of nuclear programming during carcinogenesis. |
| first_indexed | 2024-09-23T15:26:47Z |
| format | Article |
| id | mit-1721.1/100783 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:26:47Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1007832022-10-02T02:44:04Z PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells Das, Partha Pratim Hendrix, David A. Apostolou, Effie Buchner, Alice H. Canver, Matthew C. Beyaz, Semir Ljuboja, Damir Kuintzle, Rachael Kim, Woojin Karnik, Rahul Shao, Zhen Xie, Huafeng Xu, Jian De Los Angeles, Alejandro Zhang, Yingying Choe, Junho Jun, Don Leong Jia Shen, Xiaohua Gregory, Richard I. Daley, George Q. Meissner, Alexander Kellis, Manolis Hochedlinger, Konrad Kim, Jonghwan Orkin, Stuart H. Hendrix, David A. Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Hendrix, David A. Kellis, Manolis DNMT3L, a member of DNA methyltransferases family, is present only in mammals. As it provides specificity to the action of de novo methyltransferases, DNMT3A and DNMT3B and interacts with histone H3, DNMT3L has been invoked as the molecule that can read the histone code and translate it into DNA methylation. It plays an important role in the initiation of genomic imprints during gametogenesis and in nuclear reprogramming. With important functions attributed to it, it is imperative that the DNMT3L expression is tightly controlled. Previously, we had identified a CpG island within the human DNMT3L promoter and first exon that showed loss of DNA methylation in cancer samples. Here we show that this Differentially Methylated CpG island within DNMT3L (DNMT3L DMC) acts to repress transcription, is a Polycomb/Trithorax Response Element (PRE) and interacts with both PRC1 and PRC2 Polycomb repressive complexes. In addition, it adopts inactive chromatin conformation and is associated with other inactive chromatin-specific proteins like SUV39H1 and HP1. The presence of DNMT3L DMC also influences the adjacent promoter to adopt repressive histone post-translational modifications. Due to its association with multiple layers of repressive epigenetic modifications, we believe that PRE within the DNMT3L DMC is responsible for the tight regulation of DNMT3L expression and the aberrant epigenetic modifications of this region leading to DNMT3L overexpression could be the reason of nuclear programming during carcinogenesis. National Institutes of Health (U.S.) (Grant HLBI U01HL100001) 2016-01-10T21:27:39Z 2016-01-10T21:27:39Z 2015-08 2015-07 Article http://purl.org/eprint/type/JournalArticle 22111247 http://hdl.handle.net/1721.1/100783 Das, Partha Pratim, David A. Hendrix, Effie Apostolou, Alice H. Buchner, Matthew C. Canver, Semir Beyaz, Damir Ljuboja, et al. “PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells.” Cell Reports 12, no. 9 (September 2015): 1456–1470. en_US http://dx.doi.org/10.1016/j.celrep.2015.07.053 Cell Reports Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Elsevier Elsevier |
| spellingShingle | Das, Partha Pratim Hendrix, David A. Apostolou, Effie Buchner, Alice H. Canver, Matthew C. Beyaz, Semir Ljuboja, Damir Kuintzle, Rachael Kim, Woojin Karnik, Rahul Shao, Zhen Xie, Huafeng Xu, Jian De Los Angeles, Alejandro Zhang, Yingying Choe, Junho Jun, Don Leong Jia Shen, Xiaohua Gregory, Richard I. Daley, George Q. Meissner, Alexander Kellis, Manolis Hochedlinger, Konrad Kim, Jonghwan Orkin, Stuart H. Hendrix, David A. PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells |
| title | PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells |
| title_full | PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells |
| title_fullStr | PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells |
| title_full_unstemmed | PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells |
| title_short | PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells |
| title_sort | prc2 is required to maintain expression of the maternal gtl2 rian mirg locus by preventing de novo dna methylation in mouse embryonic stem cells |
| url | http://hdl.handle.net/1721.1/100783 |
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