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Histone macroH2A1.2 promotes metabolic health and leanness by inhibiting adipogenesis
by
Kiyotaka Hatsuzawa
, Asami Oji
, Michela Borghesan
, Francesc Villarroya
, Giulia Bolasco
, Valerio Pazienza
, Francesca Rappa
, Rosario Barone
, Tomoko M. Nakanishi
, Joan Villarroya
, Francesco Cappello
, Giuseppe Fusai
, Sara Cannito
, Domenico Memoli
, Concetta Panebianco
, Domenico Tamburrino
, Manlio Vinciguerra
, Roberta Tarallo
, Giuseppe Mazza
in
Adipogenesis
/ Adipose Tissue - cytology
/ Adipose Tissue - metabolism
/ Adipose tissue, Histone variants, Obesity, macroh2a1.2
/ Adipose tissue; Histone variants; macroh2a1.2; Obesity; Molecular Biology; Genetics
/ Adipose tissues
/ ADIPOSE-TISSUE
/ Analysis
/ Animal Genetics and Genomics
/ Animals
/ Biomedical and Life Sciences
/ Body Mass Index
/ CANCER
/ Cell Biology
/ Cell Differentiation
/ Cell Line
/ Cyclin-Dependent Kinase Inhibitor p21
/ Cyclin-Dependent Kinase Inhibitor p21 - genetics
/ Cyclin-Dependent Kinase Inhibitor p21 - metabolism
/ Diet, High-Fat
/ DIFFERENTIATION
/ DNA METHYLATION
/ Epigenetic inheritance
/ EPIGENETIC REGULATOR
/ FATTY LIVER-DISEASE
/ Gene Expression
/ Gene Function
/ Genetic transcription
/ Genetics
/ Genetics & Heredity
/ Glucose Tolerance Test
/ Histone variant
/ Histone variants
/ Histones
/ Histones - genetics
/ Histones - metabolism
/ Human Genetics
/ Humans
/ Insulin
/ Insulin - metabolism
/ Life Sciences
/ Life Sciences & Biomedicine
/ Liver
/ Liver - pathology
/ macroh2a1.2
/ Metabolic Engineering
/ Mice
/ Mice, Inbred C57BL
/ Mice, Transgenic
/ Molecular Biology
/ Obesity
/ Pancreas
/ Pancreas - pathology
/ Phenotype
/ Physiological aspects
/ Plant Genetics and Genomics
/ PLURIPOTENCY
/ Science & Technology
/ Skin
/ Skin - pathology
/ STEM-CELLS
/ Uncoupling Protein 1
/ Uncoupling Protein 1 - genetics
/ Uncoupling Protein 1 - metabolism
/ VARIANTS
2016
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Histone macroH2A1.2 promotes metabolic health and leanness by inhibiting adipogenesis
by
Kiyotaka Hatsuzawa
, Asami Oji
, Michela Borghesan
, Francesc Villarroya
, Giulia Bolasco
, Valerio Pazienza
, Francesca Rappa
, Rosario Barone
, Tomoko M. Nakanishi
, Joan Villarroya
, Francesco Cappello
, Giuseppe Fusai
, Sara Cannito
, Domenico Memoli
, Concetta Panebianco
, Domenico Tamburrino
, Manlio Vinciguerra
, Roberta Tarallo
, Giuseppe Mazza
in
Adipogenesis
/ Adipose Tissue - cytology
/ Adipose Tissue - metabolism
/ Adipose tissue, Histone variants, Obesity, macroh2a1.2
/ Adipose tissue; Histone variants; macroh2a1.2; Obesity; Molecular Biology; Genetics
/ Adipose tissues
/ ADIPOSE-TISSUE
/ Analysis
/ Animal Genetics and Genomics
/ Animals
/ Biomedical and Life Sciences
/ Body Mass Index
/ CANCER
/ Cell Biology
/ Cell Differentiation
/ Cell Line
/ Cyclin-Dependent Kinase Inhibitor p21
/ Cyclin-Dependent Kinase Inhibitor p21 - genetics
/ Cyclin-Dependent Kinase Inhibitor p21 - metabolism
/ Diet, High-Fat
/ DIFFERENTIATION
/ DNA METHYLATION
/ Epigenetic inheritance
/ EPIGENETIC REGULATOR
/ FATTY LIVER-DISEASE
/ Gene Expression
/ Gene Function
/ Genetic transcription
/ Genetics
/ Genetics & Heredity
/ Glucose Tolerance Test
/ Histone variant
/ Histone variants
/ Histones
/ Histones - genetics
/ Histones - metabolism
/ Human Genetics
/ Humans
/ Insulin
/ Insulin - metabolism
/ Life Sciences
/ Life Sciences & Biomedicine
/ Liver
/ Liver - pathology
/ macroh2a1.2
/ Metabolic Engineering
/ Mice
/ Mice, Inbred C57BL
/ Mice, Transgenic
/ Molecular Biology
/ Obesity
/ Pancreas
/ Pancreas - pathology
/ Phenotype
/ Physiological aspects
/ Plant Genetics and Genomics
/ PLURIPOTENCY
/ Science & Technology
/ Skin
/ Skin - pathology
/ STEM-CELLS
/ Uncoupling Protein 1
/ Uncoupling Protein 1 - genetics
/ Uncoupling Protein 1 - metabolism
/ VARIANTS
2016
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Histone macroH2A1.2 promotes metabolic health and leanness by inhibiting adipogenesis
by
Kiyotaka Hatsuzawa
, Asami Oji
, Michela Borghesan
, Francesc Villarroya
, Giulia Bolasco
, Valerio Pazienza
, Francesca Rappa
, Rosario Barone
, Tomoko M. Nakanishi
, Joan Villarroya
, Francesco Cappello
, Giuseppe Fusai
, Sara Cannito
, Domenico Memoli
, Concetta Panebianco
, Domenico Tamburrino
, Manlio Vinciguerra
, Roberta Tarallo
, Giuseppe Mazza
in
Adipogenesis
/ Adipose Tissue - cytology
/ Adipose Tissue - metabolism
/ Adipose tissue, Histone variants, Obesity, macroh2a1.2
/ Adipose tissue; Histone variants; macroh2a1.2; Obesity; Molecular Biology; Genetics
/ Adipose tissues
/ ADIPOSE-TISSUE
/ Analysis
/ Animal Genetics and Genomics
/ Animals
/ Biomedical and Life Sciences
/ Body Mass Index
/ CANCER
/ Cell Biology
/ Cell Differentiation
/ Cell Line
/ Cyclin-Dependent Kinase Inhibitor p21
/ Cyclin-Dependent Kinase Inhibitor p21 - genetics
/ Cyclin-Dependent Kinase Inhibitor p21 - metabolism
/ Diet, High-Fat
/ DIFFERENTIATION
/ DNA METHYLATION
/ Epigenetic inheritance
/ EPIGENETIC REGULATOR
/ FATTY LIVER-DISEASE
/ Gene Expression
/ Gene Function
/ Genetic transcription
/ Genetics
/ Genetics & Heredity
/ Glucose Tolerance Test
/ Histone variant
/ Histone variants
/ Histones
/ Histones - genetics
/ Histones - metabolism
/ Human Genetics
/ Humans
/ Insulin
/ Insulin - metabolism
/ Life Sciences
/ Life Sciences & Biomedicine
/ Liver
/ Liver - pathology
/ macroh2a1.2
/ Metabolic Engineering
/ Mice
/ Mice, Inbred C57BL
/ Mice, Transgenic
/ Molecular Biology
/ Obesity
/ Pancreas
/ Pancreas - pathology
/ Phenotype
/ Physiological aspects
/ Plant Genetics and Genomics
/ PLURIPOTENCY
/ Science & Technology
/ Skin
/ Skin - pathology
/ STEM-CELLS
/ Uncoupling Protein 1
/ Uncoupling Protein 1 - genetics
/ Uncoupling Protein 1 - metabolism
/ VARIANTS
2016
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Histone macroH2A1.2 promotes metabolic health and leanness by inhibiting adipogenesis
Journal Article
Histone macroH2A1.2 promotes metabolic health and leanness by inhibiting adipogenesis
2016
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Overview
Background
Obesity has tremendous impact on the health systems. Its epigenetic bases are unclear. MacroH2A1 is a variant of histone H2A, present in two alternatively exon-spliced isoforms macroH2A1.1 and macroH2A1.2, regulating cell plasticity and proliferation, during pluripotency and tumorigenesis. Their role in adipose tissue plasticity is unknown.
Results
Here, we show evidence that macroH2A1.1 protein levels in the visceral adipose tissue of obese humans positively correlate with BMI, while macroH2A1.2 is nearly absent. We thus introduced a constitutive GFP-tagged transgene for macroH2A1.2 in mice, and we characterized their metabolic health upon being fed a standard chow diet or a high fat diet. Despite unchanged food intake, these mice exhibit lower adipose mass and improved glucose metabolism both under a chow and an obesogenic diet. In the latter regimen, transgenic mice display smaller pancreatic islets and significantly less inflammation. MacroH2A1.2 overexpression in the mouse adipose tissue induced dramatic changes in the transcript levels of key adipogenic genes; genomic analyses comparing pre-adipocytes to mature adipocytes uncovered only minor changes in macroH2A1.2 genomic distribution upon adipogenic differentiation and suggested differential cooperation with transcription factors. MacroH2A1.2 overexpression markedly inhibited adipogenesis, while overexpression of macroH2A1.1 had opposite effects.
Conclusions
MacroH2A1.2 is an unprecedented chromatin component powerfully promoting metabolic health by modulating anti-adipogenic transcriptional networks in the differentiating adipose tissue. Strategies aiming at enhancing macroH2A1.2 expression might counteract excessive adiposity in humans.
Publisher
Springer Science and Business Media LLC,BioMed Central,BioMed Central Ltd,Springer Nature B.V
Subject
/ Adipose tissue, Histone variants, Obesity, macroh2a1.2
/ Adipose tissue; Histone variants; macroh2a1.2; Obesity; Molecular Biology; Genetics
/ Analysis
/ Animal Genetics and Genomics
/ Animals
/ Biomedical and Life Sciences
/ CANCER
/ Cyclin-Dependent Kinase Inhibitor p21
/ Cyclin-Dependent Kinase Inhibitor p21 - genetics
/ Cyclin-Dependent Kinase Inhibitor p21 - metabolism
/ Genetics
/ Histones
/ Humans
/ Insulin
/ Liver
/ Mice
/ Obesity
/ Pancreas
/ Skin
/ Uncoupling Protein 1 - genetics
/ Uncoupling Protein 1 - metabolism
/ VARIANTS
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