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Epigenetic inheritance of circadian period in clonal cells
Circadian oscillations are generated via transcriptional-translational negative feedback loops. However, individual cells from fibroblast cell lines have heterogeneous rhythms, oscillating independently and with different period lengths. Here we showed that heterogeneity in circadian period is herit...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289596/ https://www.ncbi.nlm.nih.gov/pubmed/32459177 http://dx.doi.org/10.7554/eLife.54186 |
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author | Li, Yan Shan, Yongli Kilaru, Gokhul Krishna Berto, Stefano Wang, Guang-Zhong Cox, Kimberly H Yoo, Seung-Hee Yang, Shuzhang Konopka, Genevieve Takahashi, Joseph S |
author_facet | Li, Yan Shan, Yongli Kilaru, Gokhul Krishna Berto, Stefano Wang, Guang-Zhong Cox, Kimberly H Yoo, Seung-Hee Yang, Shuzhang Konopka, Genevieve Takahashi, Joseph S |
author_sort | Li, Yan |
collection | PubMed |
description | Circadian oscillations are generated via transcriptional-translational negative feedback loops. However, individual cells from fibroblast cell lines have heterogeneous rhythms, oscillating independently and with different period lengths. Here we showed that heterogeneity in circadian period is heritable and used a multi-omics approach to investigate underlying mechanisms. By examining large-scale phenotype-associated gene expression profiles in hundreds of mouse clonal cell lines, we identified and validated multiple novel candidate genes involved in circadian period determination in the absence of significant genomic variants. We also discovered differentially co-expressed gene networks that were functionally associated with period length. We further demonstrated that global differential DNA methylation bidirectionally regulated these same gene networks. Interestingly, we found that depletion of DNMT1 and DNMT3A had opposite effects on circadian period, suggesting non-redundant roles in circadian gene regulation. Together, our findings identify novel gene candidates involved in periodicity, and reveal DNA methylation as an important regulator of circadian periodicity. |
format | Online Article Text |
id | pubmed-7289596 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-72895962020-06-15 Epigenetic inheritance of circadian period in clonal cells Li, Yan Shan, Yongli Kilaru, Gokhul Krishna Berto, Stefano Wang, Guang-Zhong Cox, Kimberly H Yoo, Seung-Hee Yang, Shuzhang Konopka, Genevieve Takahashi, Joseph S eLife Neuroscience Circadian oscillations are generated via transcriptional-translational negative feedback loops. However, individual cells from fibroblast cell lines have heterogeneous rhythms, oscillating independently and with different period lengths. Here we showed that heterogeneity in circadian period is heritable and used a multi-omics approach to investigate underlying mechanisms. By examining large-scale phenotype-associated gene expression profiles in hundreds of mouse clonal cell lines, we identified and validated multiple novel candidate genes involved in circadian period determination in the absence of significant genomic variants. We also discovered differentially co-expressed gene networks that were functionally associated with period length. We further demonstrated that global differential DNA methylation bidirectionally regulated these same gene networks. Interestingly, we found that depletion of DNMT1 and DNMT3A had opposite effects on circadian period, suggesting non-redundant roles in circadian gene regulation. Together, our findings identify novel gene candidates involved in periodicity, and reveal DNA methylation as an important regulator of circadian periodicity. eLife Sciences Publications, Ltd 2020-05-27 /pmc/articles/PMC7289596/ /pubmed/32459177 http://dx.doi.org/10.7554/eLife.54186 Text en © 2020, Li et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Neuroscience Li, Yan Shan, Yongli Kilaru, Gokhul Krishna Berto, Stefano Wang, Guang-Zhong Cox, Kimberly H Yoo, Seung-Hee Yang, Shuzhang Konopka, Genevieve Takahashi, Joseph S Epigenetic inheritance of circadian period in clonal cells |
title | Epigenetic inheritance of circadian period in clonal cells |
title_full | Epigenetic inheritance of circadian period in clonal cells |
title_fullStr | Epigenetic inheritance of circadian period in clonal cells |
title_full_unstemmed | Epigenetic inheritance of circadian period in clonal cells |
title_short | Epigenetic inheritance of circadian period in clonal cells |
title_sort | epigenetic inheritance of circadian period in clonal cells |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289596/ https://www.ncbi.nlm.nih.gov/pubmed/32459177 http://dx.doi.org/10.7554/eLife.54186 |
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