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Epigenetic regulation of the circadian clock: role of 5-aza-2′-deoxycytidine

We have been investigating transcriptional regulation of the BMAL1 gene, a critical component of the mammalian clock system including DNA methylation. Here, a more detailed analysis of the regulation of DNA methylation of BMAL1 proceeded in RPMI8402 lymphoma cells. We found that CpG islands in the B...

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Autores principales: Tomita, Tatsunosuke, Kurita, Ryoji, Onishi, Yoshiaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437938/
https://www.ncbi.nlm.nih.gov/pubmed/28487473
http://dx.doi.org/10.1042/BSR20170053
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author Tomita, Tatsunosuke
Kurita, Ryoji
Onishi, Yoshiaki
author_facet Tomita, Tatsunosuke
Kurita, Ryoji
Onishi, Yoshiaki
author_sort Tomita, Tatsunosuke
collection PubMed
description We have been investigating transcriptional regulation of the BMAL1 gene, a critical component of the mammalian clock system including DNA methylation. Here, a more detailed analysis of the regulation of DNA methylation of BMAL1 proceeded in RPMI8402 lymphoma cells. We found that CpG islands in the BMAL1 and the PER2 promoters were hyper- and hypomethylated, respectively and that 5-aza-2′-deoxycytidine (aza-dC) not only enhanced PER2 gene expression but also PER2 oscillation within 24 h in RPMI8402 cells. That is, such hypermethylation of CpG islands in the BMAL1 promoter restricted PER2 expression which was recovered by aza-dC within 1 day in these cells. These results suggest that the circadian clock system can be recovered through BMAL1 expression induced by aza-dC within a day. The RPIB9 promoter of RPMI8402 cells, which is a methylation hotspot in lymphoblastic leukemia, was also hypermethylated and aza-dC gradually recovered RPIB9 expression in 3 days. In addition, methylation-specific PCR revealed a different degree of aza-dC-induced methylation release between BMAL1 and RPIB9. These results suggest that the aza-dC-induced recovery of gene expression from DNA methylation is dependent on a gene, for example the rapid response to demethylation by the circadian system, and thus, is of importance to clinical strategies for treating cancer.
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spelling pubmed-54379382017-06-01 Epigenetic regulation of the circadian clock: role of 5-aza-2′-deoxycytidine Tomita, Tatsunosuke Kurita, Ryoji Onishi, Yoshiaki Biosci Rep Research Articles We have been investigating transcriptional regulation of the BMAL1 gene, a critical component of the mammalian clock system including DNA methylation. Here, a more detailed analysis of the regulation of DNA methylation of BMAL1 proceeded in RPMI8402 lymphoma cells. We found that CpG islands in the BMAL1 and the PER2 promoters were hyper- and hypomethylated, respectively and that 5-aza-2′-deoxycytidine (aza-dC) not only enhanced PER2 gene expression but also PER2 oscillation within 24 h in RPMI8402 cells. That is, such hypermethylation of CpG islands in the BMAL1 promoter restricted PER2 expression which was recovered by aza-dC within 1 day in these cells. These results suggest that the circadian clock system can be recovered through BMAL1 expression induced by aza-dC within a day. The RPIB9 promoter of RPMI8402 cells, which is a methylation hotspot in lymphoblastic leukemia, was also hypermethylated and aza-dC gradually recovered RPIB9 expression in 3 days. In addition, methylation-specific PCR revealed a different degree of aza-dC-induced methylation release between BMAL1 and RPIB9. These results suggest that the aza-dC-induced recovery of gene expression from DNA methylation is dependent on a gene, for example the rapid response to demethylation by the circadian system, and thus, is of importance to clinical strategies for treating cancer. Portland Press Ltd. 2017-05-19 /pmc/articles/PMC5437938/ /pubmed/28487473 http://dx.doi.org/10.1042/BSR20170053 Text en © 2017 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
Tomita, Tatsunosuke
Kurita, Ryoji
Onishi, Yoshiaki
Epigenetic regulation of the circadian clock: role of 5-aza-2′-deoxycytidine
title Epigenetic regulation of the circadian clock: role of 5-aza-2′-deoxycytidine
title_full Epigenetic regulation of the circadian clock: role of 5-aza-2′-deoxycytidine
title_fullStr Epigenetic regulation of the circadian clock: role of 5-aza-2′-deoxycytidine
title_full_unstemmed Epigenetic regulation of the circadian clock: role of 5-aza-2′-deoxycytidine
title_short Epigenetic regulation of the circadian clock: role of 5-aza-2′-deoxycytidine
title_sort epigenetic regulation of the circadian clock: role of 5-aza-2′-deoxycytidine
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437938/
https://www.ncbi.nlm.nih.gov/pubmed/28487473
http://dx.doi.org/10.1042/BSR20170053
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