Histone macroH2A1.2 promotes metabolic health and leanness by inhibiting adipogenesis

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F16%3A00065824" target="_blank" >RIV/00159816:_____/16:00065824 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1186/s13072-016-0098-9" target="_blank" >http://dx.doi.org/10.1186/s13072-016-0098-9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s13072-016-0098-9" target="_blank" >10.1186/s13072-016-0098-9</a>

Result language

angličtina

Original language name

Histone macroH2A1.2 promotes metabolic health and leanness by inhibiting adipogenesis

Original language description

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.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Epigenetics &amp; Chromatin

ISSN

1756-8935

e-ISSN

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Volume of the periodical

9

Issue of the periodical within the volume

OCT

Country of publishing house

GB - UNITED KINGDOM

Number of pages

19

Pages from-to

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UT code for WoS article

000385970400001

EID of the result in the Scopus database

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