Cargando…
H19 lncRNA alters DNA methylation genome wide by regulating S-adenosylhomocysteine hydrolase
DNA methylation is essential for mammalian development and physiology. Here we report that the developmentally regulated H19 lncRNA binds to and inhibits S-adenosylhomocysteine hydrolase (SAHH), the only mammalian enzyme capable of hydrolysing S-adenosylhomocysteine (SAH). SAH is a potent feedback i...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703905/ https://www.ncbi.nlm.nih.gov/pubmed/26687445 http://dx.doi.org/10.1038/ncomms10221 |
_version_ | 1782408803994566656 |
---|---|
author | Zhou, Jichun Yang, Lihua Zhong, Tianyu Mueller, Martin Men, Yi Zhang, Na Xie, Juanke Giang, Karolyn Chung, Hunter Sun, Xueguang Lu, Lingeng Carmichael, Gordon G Taylor, Hugh S Huang, Yingqun |
author_facet | Zhou, Jichun Yang, Lihua Zhong, Tianyu Mueller, Martin Men, Yi Zhang, Na Xie, Juanke Giang, Karolyn Chung, Hunter Sun, Xueguang Lu, Lingeng Carmichael, Gordon G Taylor, Hugh S Huang, Yingqun |
author_sort | Zhou, Jichun |
collection | PubMed |
description | DNA methylation is essential for mammalian development and physiology. Here we report that the developmentally regulated H19 lncRNA binds to and inhibits S-adenosylhomocysteine hydrolase (SAHH), the only mammalian enzyme capable of hydrolysing S-adenosylhomocysteine (SAH). SAH is a potent feedback inhibitor of S-adenosylmethionine (SAM)-dependent methyltransferases that methylate diverse cellular components, including DNA, RNA, proteins, lipids and neurotransmitters. We show that H19 knockdown activates SAHH, leading to increased DNMT3B-mediated methylation of an lncRNA-encoding gene Nctc1 within the Igf2-H19-Nctc1 locus. Genome-wide methylation profiling reveals methylation changes at numerous gene loci consistent with SAHH modulation by H19. Our results uncover an unanticipated regulatory circuit involving broad epigenetic alterations by a single abundantly expressed lncRNA that may underlie gene methylation dynamics of development and diseases and suggest that this mode of regulation may extend to other cellular components. |
format | Online Article Text |
id | pubmed-4703905 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47039052016-01-22 H19 lncRNA alters DNA methylation genome wide by regulating S-adenosylhomocysteine hydrolase Zhou, Jichun Yang, Lihua Zhong, Tianyu Mueller, Martin Men, Yi Zhang, Na Xie, Juanke Giang, Karolyn Chung, Hunter Sun, Xueguang Lu, Lingeng Carmichael, Gordon G Taylor, Hugh S Huang, Yingqun Nat Commun Article DNA methylation is essential for mammalian development and physiology. Here we report that the developmentally regulated H19 lncRNA binds to and inhibits S-adenosylhomocysteine hydrolase (SAHH), the only mammalian enzyme capable of hydrolysing S-adenosylhomocysteine (SAH). SAH is a potent feedback inhibitor of S-adenosylmethionine (SAM)-dependent methyltransferases that methylate diverse cellular components, including DNA, RNA, proteins, lipids and neurotransmitters. We show that H19 knockdown activates SAHH, leading to increased DNMT3B-mediated methylation of an lncRNA-encoding gene Nctc1 within the Igf2-H19-Nctc1 locus. Genome-wide methylation profiling reveals methylation changes at numerous gene loci consistent with SAHH modulation by H19. Our results uncover an unanticipated regulatory circuit involving broad epigenetic alterations by a single abundantly expressed lncRNA that may underlie gene methylation dynamics of development and diseases and suggest that this mode of regulation may extend to other cellular components. Nature Publishing Group 2015-12-21 /pmc/articles/PMC4703905/ /pubmed/26687445 http://dx.doi.org/10.1038/ncomms10221 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Zhou, Jichun Yang, Lihua Zhong, Tianyu Mueller, Martin Men, Yi Zhang, Na Xie, Juanke Giang, Karolyn Chung, Hunter Sun, Xueguang Lu, Lingeng Carmichael, Gordon G Taylor, Hugh S Huang, Yingqun H19 lncRNA alters DNA methylation genome wide by regulating S-adenosylhomocysteine hydrolase |
title | H19 lncRNA alters DNA methylation genome wide by regulating S-adenosylhomocysteine hydrolase |
title_full | H19 lncRNA alters DNA methylation genome wide by regulating S-adenosylhomocysteine hydrolase |
title_fullStr | H19 lncRNA alters DNA methylation genome wide by regulating S-adenosylhomocysteine hydrolase |
title_full_unstemmed | H19 lncRNA alters DNA methylation genome wide by regulating S-adenosylhomocysteine hydrolase |
title_short | H19 lncRNA alters DNA methylation genome wide by regulating S-adenosylhomocysteine hydrolase |
title_sort | h19 lncrna alters dna methylation genome wide by regulating s-adenosylhomocysteine hydrolase |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703905/ https://www.ncbi.nlm.nih.gov/pubmed/26687445 http://dx.doi.org/10.1038/ncomms10221 |
work_keys_str_mv | AT zhoujichun h19lncrnaaltersdnamethylationgenomewidebyregulatingsadenosylhomocysteinehydrolase AT yanglihua h19lncrnaaltersdnamethylationgenomewidebyregulatingsadenosylhomocysteinehydrolase AT zhongtianyu h19lncrnaaltersdnamethylationgenomewidebyregulatingsadenosylhomocysteinehydrolase AT muellermartin h19lncrnaaltersdnamethylationgenomewidebyregulatingsadenosylhomocysteinehydrolase AT menyi h19lncrnaaltersdnamethylationgenomewidebyregulatingsadenosylhomocysteinehydrolase AT zhangna h19lncrnaaltersdnamethylationgenomewidebyregulatingsadenosylhomocysteinehydrolase AT xiejuanke h19lncrnaaltersdnamethylationgenomewidebyregulatingsadenosylhomocysteinehydrolase AT giangkarolyn h19lncrnaaltersdnamethylationgenomewidebyregulatingsadenosylhomocysteinehydrolase AT chunghunter h19lncrnaaltersdnamethylationgenomewidebyregulatingsadenosylhomocysteinehydrolase AT sunxueguang h19lncrnaaltersdnamethylationgenomewidebyregulatingsadenosylhomocysteinehydrolase AT lulingeng h19lncrnaaltersdnamethylationgenomewidebyregulatingsadenosylhomocysteinehydrolase AT carmichaelgordong h19lncrnaaltersdnamethylationgenomewidebyregulatingsadenosylhomocysteinehydrolase AT taylorhughs h19lncrnaaltersdnamethylationgenomewidebyregulatingsadenosylhomocysteinehydrolase AT huangyingqun h19lncrnaaltersdnamethylationgenomewidebyregulatingsadenosylhomocysteinehydrolase |