DNA methylation in AgRP neurons regulates voluntary exercise behavior in mice

Mackay, Harry A.; Scott, C. Anthony; Duryea, Jack D.; Baker, Maria S.; Laritsky, Eleonora; Elson, Amanda E.T.; Garland, Theodore; Fiorotto, Marta L.; Chen, Rui; Li, Yumei; Coarfa, Cristian; Simerly, Richard B.; Waterland, Robert A.

doi:10.1038/s41467-019-13339-3

Cited by 30 publications

(34 citation statements)

References 60 publications

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“…These observations are not surprising, as [ 10 ] investigated epigenetic changes occurring in mature neurons using transgenic mice. We noticed several studies used the term FACS while describing nuclei sorting (i.e., FANS) [ 39 , 40 , 41 , 42 , 43 ]. It is reasonable that FACS will remain as general term for flow cytometry sorting; however, it is important to emphasize the material sorted and use appropriate terminology when required (e.g., FANS for nuclei sorting).…”

Section: Discussionmentioning

confidence: 99%

INTACT vs. FANS for Cell-Type-Specific Nuclei Sorting: A Comprehensive Qualitative and Quantitative Comparison

Chongtham

Butto

Mungikar

et al. 2021

IJMS

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Increasing numbers of studies seek to characterize the different cellular sub-populations present in mammalian tissues. The techniques “Isolation of Nuclei Tagged in Specific Cell Types” (INTACT) or “Fluorescence-Activated Nuclei Sorting” (FANS) are frequently used for isolating nuclei of specific cellular subtypes. These nuclei are then used for molecular characterization of the cellular sub-populations. Despite the increasing popularity of both techniques, little is known about their isolation efficiency, advantages, and disadvantages or downstream molecular effects. In our study, we compared the physical and molecular attributes of sfGFP+ nuclei isolated by the two methods—INTACT and FANS—from the neocortices of Arc-CreERT2 × CAG-Sun1/sfGFP animals. We identified differences in efficiency of sfGFP+ nuclei isolation, nuclear size as well as transcriptional (RNA-seq) and chromatin accessibility (ATAC-seq) states. Therefore, our study presents a comprehensive comparison between the two widely used nuclei sorting techniques, identifying the advantages and disadvantages for both INTACT and FANS. Our conclusions are summarized in a table to guide researchers in selecting the most suitable methodology for their individual experimental design.

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Section: Discussionmentioning

confidence: 99%

INTACT vs. FANS for Cell-Type-Specific Nuclei Sorting: A Comprehensive Qualitative and Quantitative Comparison

Chongtham

Butto

Mungikar

et al. 2021

IJMS

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“…In addition to enabling such novel theoretical insights, CluBCpG has many potential practical applications. An early version of this approach was successfully utilized to infer cell type-specific methylation differences among mouse hypothalamic neurons, a subset of which were affected by cell type-specific knockout of Dnmt3a [38]. With sufficient highquality WGBS data to construct cell type-specific references, CluBCpG could be utilized to develop a new state-of-the-art, highly accurate cellular deconvolution approach.…”

Section: Discussionmentioning

confidence: 99%

Identification of cell type-specific methylation signals in bulk whole genome bisulfite sequencing data

et al. 2020

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Background: The traditional approach to studying the epigenetic mechanism CpG methylation in tissue samples is to identify regions of concordant differential methylation spanning multiple CpG sites (differentially methylated regions). Variation limited to single or small numbers of CpGs has been assumed to reflect stochastic processes. To test this, we developed software, Cluster-Based analysis of CpG methylation (CluBCpG), and explored variation in read-level CpG methylation patterns in whole genome bisulfite sequencing data. Results: Analysis of both human and mouse whole genome bisulfite sequencing datasets reveals read-level signatures associated with cell type and cell type-specific biological processes. These signatures, which are mostly orthogonal to classical differentially methylated regions, are enriched at cell type-specific enhancers and allow estimation of proportional cell composition in synthetic mixtures and improved prediction of gene expression. In tandem, we developed a machine learning algorithm, Precise Read-Level Imputation of Methylation (PReLIM), to increase coverage of existing whole genome bisulfite sequencing datasets by imputing CpG methylation states on individual sequencing reads. PReLIM both improves CluBCpG coverage and performance and enables identification of novel differentially methylated regions, which we independently validate. Conclusions: Our data indicate that, rather than stochastic variation, read-level CpG methylation patterns in tissue whole genome bisulfite sequencing libraries reflect cell type. Accordingly, these new computational tools should lead to an improved understanding of epigenetic regulation by DNA methylation.

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“…In reality, DNAm can influence motor abilities and modulate behaviors reversely to sustain normal movements. For example, deletion of DNMT3a in AgRP neurons can reduce voluntary exercise behavior by disrupting the expression of genes that are characteristic of AgRP neurons in the arcuate nucleus of the hypothalamus [ 158 ].…”

Section: Epigenetic Modulation To Reverse Motor Deficitsmentioning

confidence: 99%

Roles of physical exercise in neurodegeneration: reversal of epigenetic clock

Zhu

Liu

et al. 2021

Transl Neurodegener

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The epigenetic clock is defined by the DNA methylation (DNAm) level and has been extensively applied to distinguish biological age from chronological age. Aging-related neurodegeneration is associated with epigenetic alteration, which determines the status of diseases. In recent years, extensive research has shown that physical exercise (PE) can affect the DNAm level, implying a reversal of the epigenetic clock in neurodegeneration. PE also regulates brain plasticity, neuroinflammation, and molecular signaling cascades associated with epigenetics. This review summarizes the effects of PE on neurodegenerative diseases via both general and disease-specific DNAm mechanisms, and discusses epigenetic modifications that alleviate the pathological symptoms of these diseases. This may lead to probing of the underpinnings of neurodegenerative disorders and provide valuable therapeutic references for cognitive and motor dysfunction.

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DNA methylation in AgRP neurons regulates voluntary exercise behavior in mice

Cited by 30 publications

References 60 publications

INTACT vs. FANS for Cell-Type-Specific Nuclei Sorting: A Comprehensive Qualitative and Quantitative Comparison

INTACT vs. FANS for Cell-Type-Specific Nuclei Sorting: A Comprehensive Qualitative and Quantitative Comparison

Identification of cell type-specific methylation signals in bulk whole genome bisulfite sequencing data

Roles of physical exercise in neurodegeneration: reversal of epigenetic clock

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