Dataset Information

Integrative epigenomic and transcriptomic analyses reveal metabolic switching by intermittent fasting in brain.

ABSTRACT: Intermittent fasting (IF) remains the most effective intervention to achieve robust anti-aging effects and attenuation of age-related diseases in various species. Epigenetic modifications mediate the biological effects of several environmental factors on gene expression; however, no information is available on the effects of IF on the epigenome. Here, we first found that IF for 3 months caused modulation of H3K9 trimethylation (H3K9me₃) in the cerebellum, which in turn orchestrated a plethora of transcriptomic changes involved in robust metabolic switching processes commonly observed during IF. Second, a portion of both the epigenomic and transcriptomic modulations induced by IF was remarkably preserved for at least 3 months post-IF refeeding, indicating that memory of IF-induced epigenetic changes was maintained. Notably, though, we found that termination of IF resulted in a loss of H3K9me₃ regulation of the transcriptome. Collectively, our study characterizes the novel effects of IF on the epigenetic-transcriptomic axis, which controls myriad metabolic processes. The comprehensive analyses undertaken in this study reveal a molecular framework for understanding how IF impacts the metabolo-epigenetic axis of the brain and will serve as a valuable resource for future research.

SUBMITTER: Ng GY

PROVIDER: S-EPMC9617005 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Integrative epigenomic and transcriptomic analyses reveal metabolic switching by intermittent fasting in brain.

Ng Gavin Yong-Quan GY Sheng Dominic Paul Lee Kok DPLK Bae Han-Gyu HG Kang Sung Wook SW Fann David Yang-Wei DY Park Jinsu J Kim Joonki J Alli-Shaik Asfa A Lee Jeongmi J Kim Eunae E Park Sunyoung S Han Jeung-Whan JW Karamyan Vardan V Okun Eitan E Dheen Thameem T Hande Manoor Prakash MP Vemuganti Raghu R Mallilankaraman Karthik K Lim Lina H K LHK Kennedy Brian K BK Drummond Grant R GR Sobey Christopher G CG Gunaratne Jayantha J Mattson Mark P MP Foo Roger Sik-Yin RS Jo Dong-Gyu DG Arumugam Thiruma V TV

GeroScience 20220331 4

Intermittent fasting (IF) remains the most effective intervention to achieve robust anti-aging effects and attenuation of age-related diseases in various species. Epigenetic modifications mediate the biological effects of several environmental factors on gene expression; however, no information is available on the effects of IF on the epigenome. Here, we first found that IF for 3 months caused modulation of H3K9 trimethylation (H3K9me<sub>3</sub>) in the cerebellum, which in turn orchestrated a ...[more]

PMID: 35357643

Similar Datasets

Project description:While recent integrative analyses of copy number and gene expression data in breast cancer have revealed a complex molecular landscape with multiple subtypes and many oncogenic/tumour suppressor driver events, much less is known about the role of DNA methylation in shaping breast cancer taxonomy and defining driver events.Here, we applied a powerful integrative network algorithm to matched DNA methylation and RNA-Seq data for 724 estrogen receptor (ER)-positive (ER+) breast cancers and 111 normal adjacent tissue specimens from The Cancer Genome Atlas (TCGA) project, in order to identify putative epigenetic driver events and to explore the resulting molecular taxonomy. This revealed the existence of nine functionally deregulated epigenetic hotspots encompassing a total of 146 genes, which we were able to validate in independent data sets encompassing over 1000 ER+ breast cancers. Integrative clustering of the matched messenger RNA (mRNA) and DNA methylation data over these genes resulted in only two clusters, which correlated very strongly with the luminal-A and luminal B subtypes. Overall, luminal-A and luminal-B breast cancers shared the same epigenetically deregulated hotspots but with luminal-B cancers exhibiting increased aberrant DNA methylation patterns relative to normal tissue. We show that increased levels of DNA methylation and mRNA expression deviation from the normal state define a marker of poor prognosis. Our data further implicates epigenetic silencing of WNT signalling antagonists and bone morphogenetic proteins (BMP) as key events underlying both luminal subtypes but specially of luminal-B breast cancer. Finally, we show that DNA methylation changes within the identified epigenetic interactome hotspots do not exhibit mutually exclusive patterns within the same cancer sample, instead exhibiting coordinated changes within the sample.Our results indicate that the integrative DNA methylation and transcriptomic landscape of ER+ breast cancer is surprisingly homogeneous, defining two main subtypes which strongly correlate with luminal-A/B subtype status. In particular, we identify WNT and BMP signalling as key epigenetically deregulated tumour suppressor pathways in luminal ER+ breast cancer, with increased deregulation seen in luminal-B breast cancer.

Dataset Information

Integrative epigenomic and transcriptomic analyses reveal metabolic switching by intermittent fasting in brain.

Publications

Integrative epigenomic and transcriptomic analyses reveal metabolic switching by intermittent fasting in brain.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets