Subsets of Visceral Adipose Tissue Nuclei with Distinct Levels of 5-Hydroxymethylcytosine

Autor: Robert J. Schmitz, Ping Yu, Lexiang Ji, Suresh Ambati, Kevin Lee, Chuan He, Richard B. Meagher, Miao Yu, Clifton A. Baile, Elizabeth C. McKinney, Crystal L. Jackson
Rok vydání: 2016
Předmět:
0301 basic medicine
Sus scrofa
lcsh:Medicine
Fluorescent Antibody Technique
Adipose tissue
Biochemistry
Histones
chemistry.chemical_compound
Animal Cells
Adipocyte
Histone methylation
Gene expression
Adipocytes
Medicine and Health Sciences
lcsh:Science
Connective Tissue Cells
Staining
DNA methylation
Multidisciplinary
biology
Nucleotides
Organic Compounds
Cell Cycle
Flow Cytometry
Chromatin
Nucleic acids
Chemistry
medicine.anatomical_structure
Histone
Adipose Tissue
Connective Tissue
Physical Sciences
5-Methylcytosine
Epigenetics
Cellular Types
Anatomy
DNA modification
Chromatin modification
Research Article
Chromosome biology
Pluripotent Stem Cells
Intra-Abdominal Fat
Research and Analysis Methods
Cytosine
03 medical and health sciences
DNA-binding proteins
Genetics
medicine
Animals
RNA
Messenger
Cell Nucleus
Base Sequence
Gene Expression Profiling
lcsh:R
Organic Chemistry
Chemical Compounds
DAPI staining
Biology and Life Sciences
Proteins
Cell Biology
DNA
Molecular biology
Nuclear Staining
PPAR gamma
Cell nucleus
Biological Tissue
Pyrimidines
030104 developmental biology
chemistry
Specimen Preparation and Treatment
biology.protein
lcsh:Q
Biomarkers
Zdroj: PLoS ONE
PLoS ONE, Vol 11, Iss 5, p e0154949 (2016)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0154949
Popis: The reprogramming of cellular memory in specific cell types, and in visceral adipocytes in particular, appears to be a fundamental aspect of obesity and its related negative health outcomes. We explored the hypothesis that adipose tissue contains epigenetically distinct subpopulations of adipocytes that are differentially potentiated to record cellular memories of their environment. Adipocytes are large, fragile, and technically difficult to efficiently isolate and fractionate. We developed fluorescence nuclear cytometry (FNC) and fluorescence activated nuclear sorting (FANS) of cellular nuclei from visceral adipose tissue (VAT) using the levels of the pan-adipocyte protein, peroxisome proliferator-activated receptor gamma-2 (PPARg2), to distinguish classes of PPARg2-Positive (PPARg2-Pos) adipocyte nuclei from PPARg2-Negative (PPARg2-Neg) leukocyte and endothelial cell nuclei. PPARg2-Pos nuclei were 10-fold enriched for most adipocyte marker transcripts relative to PPARg2-Neg nuclei. PPARg2-Pos nuclei showed 2- to 50-fold higher levels of transcripts encoding most of the chromatin-remodeling factors assayed, which regulate the methylation of histones and DNA cytosine (e.g., DNMT1, TET1, TET2, KDM4A, KMT2C, SETDB1, PAXIP1, ARID1A, JMJD6, CARM1, and PRMT5). PPARg2-Pos nuclei were large with decondensed chromatin. TAB-seq demonstrated 5-hydroxymethylcytosine (5hmC) levels were remarkably dynamic in gene bodies of various classes of VAT nuclei, dropping 3.8-fold from the highest quintile of expressed genes to the lowest. In short, VAT-derived adipocytes appear to be more actively remodeling their chromatin than non-adipocytes.
Databáze: OpenAIRE
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