A whole lifespan mouse multi-tissue DNA methylation clock
- Brigham and Women's Hospital, Harvard Medical School, United States
Abstract
Age predictors based on DNA methylation levels at a small set of CpG sites, DNAm clocks, have been developed for humans and extended to several other species. Three currently available versions of mouse DNAm clocks were either created for individual tissues or tuned towards young ages. Here, we constructed a robust multi-tissue age predictor based on 435 CpG sites, which covers the entire mouse lifespan and remains unbiased with respect to any particular age group. It can successfully detect the effects of certain lifespan-modulating interventions on DNAm age as well as the rejuvenation effect related to the transition from fibroblasts to iPSCs. We have carried out comparative analyses of available mouse DNAm clocks, which revealed their broad applicability, but also certain limitations to the use of tissue-specific and multi-tissue age predictors. Together, these tools should help address diverse questions in aging research.
Data availability
Sequencing data have been deposited in GEO under accession code GSE121141
-
DNA methylation of mouse tissuesNCBI Gene Expression Omnibus, GSE121141.
Article and author information
Author details
Funding
National Institute on Aging (AG021518)
- Vadim N Gladyshev
National Institute on Aging (AG047200)
- Vadim N Gladyshev
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Meer et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 7,596
- views
-
- 880
- downloads
-
- 155
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
A whole lifespan mouse multi-tissue DNA methylation clock
eLife 7:e40675.
https://doi.org/10.7554/eLife.40675
Further reading
-
- Chromosomes and Gene Expression
Specialized magnetic beads that bind target proteins to a cryogenic electron microscopy grid make it possible to study the structure of protein complexes from dilute samples.
-
- Chromosomes and Gene Expression
- Structural Biology and Molecular Biophysics
Type II nuclear receptors (T2NRs) require heterodimerization with a common partner, the retinoid X receptor (RXR), to bind cognate DNA recognition sites in chromatin. Based on previous biochemical and overexpression studies, binding of T2NRs to chromatin is proposed to be regulated by competition for a limiting pool of the core RXR subunit. However, this mechanism has not yet been tested for endogenous proteins in live cells. Using single-molecule tracking (SMT) and proximity-assisted photoactivation (PAPA), we monitored interactions between endogenously tagged RXR and retinoic acid receptor (RAR) in live cells. Unexpectedly, we find that higher expression of RAR, but not RXR, increases heterodimerization and chromatin binding in U2OS cells. This surprising finding indicates the limiting factor is not RXR but likely its cadre of obligate dimer binding partners. SMT and PAPA thus provide a direct way to probe which components are functionally limiting within a complex TF interaction network providing new insights into mechanisms of gene regulation in vivo with implications for drug development targeting nuclear receptors.
