ArticleEpigenetics & chromatin2024
Histone proteoform analysis reveals epigenetic changes in adult mouse brown adipose tissue in response to cold stress.
Article in Epigenetics & chromatin, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- Quantitative Top-Down Proteomics Reveals Significant Differences in Histone Proteoforms Between Metastatic and Nonmetastatic Colorectal Cancer Cells.Proteomics · 2025Article
- Climate Change, Air Pollution and the Global Obesity Syndemic: a Review of Current Evidence.Current obesity reports · 2025Review
- The multifaceted regulation of white adipose tissue browning and their therapeutic potential.Journal of physiology and biochemistry · 2025Review
- Cold Exposure Induces Swine Brown Adipocytes to Display an Island-like Distribution with Atypical Characteristics.International journal of molecular sciences · 2025Article
- Molecular mediators of cold adaptation in mammalian cells.Communications biology · 2025Review
- Cold-Induced DHRS4 Promotes Thermogenesis via Enhanced Fatty Acid β-Oxidation in Porcine Subcutaneous Adipocytes.Animals : an open access journal from MDPI · 2025Article
- Normalized and Directional Interplay Scoring for the Interrogation of Proteoform Data.Journal of proteome research · 2025Article
- Epigenetics in evolution and adaptation to environmental challenges: pathways for disease prevention and treatment.Epigenomics · 2025Review
- Single-nucleus RNA sequencing reveals dynamic changes in the microenvironment of visceral adipose tissue and metabolic characteristics after cold exposure.Frontiers in endocrinology · 2025Article
- Unraveling Posttranslational Modification Complexity: Advances in Quantitative Histone Proteoform Mass Spectrometry.Mass spectrometry reviewsReview
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundRegulation of the thermogenic response by brown adipose tissue (BAT) is an important component of energy homeostasis with implications for the treatment of obesity and diabetes. Our preliminary analyses of RNA-Seq data uncovered many nodes representing epigenetic modifiers that are altered in BAT in response to chronic thermogenic activation. Thus, we hypothesized that chronic thermogenic activation broadly alters epigenetic modifications of DNA and histones in BAT.
resultsMotivated to understand how BAT function is regulated epigenetically, we developed a novel method for the first-ever unbiased top-down proteomic quantitation of histone modifications in BAT and validated our results with a multi-omic approach. To test our hypothesis, wildtype male C57BL/6J mice were housed under chronic conditions of thermoneutral temperature (TN, 28°C), mild cold/room temperature (RT, 22°C), or severe cold (SC, 8°C) and BAT was analyzed for DNA methylation and histone modifications. Methylation of promoters and intragenic regions in genomic DNA decrease in response to chronic cold exposure. Integration of DNA methylation and RNA expression datasets suggest a role for epigenetic modification of DNA in regulation of gene expression in response to cold. In response to cold housing, we observe increased bulk acetylation of histones H3.2 and H4, increased histone H3.2 proteoforms with di- and trimethylation of lysine 9 (K9me2 and K9me3), and increased histone H4 proteoforms with acetylation of lysine 16 (K16ac) in BAT.
conclusionsOur results reveal global epigenetically-regulated transcriptional "on" and "off" signals in murine BAT in response to varying degrees of chronic cold stimuli and establish a novel methodology to quantitatively study histones in BAT, allowing for direct comparisons to decipher mechanistic changes during the thermogenic response. Additionally, we make histone PTM and proteoform quantitation, RNA splicing, RRBS, and transcriptional footprint datasets available as a resource for future research.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.