Depletion of Nsd2-mediated histone H3K36 methylation impairs adipose tissue development and function

The epigenetic mechanisms regulating adipose tissue development and function are poorly understood. In this study, we show that depletion of histone H3K36 methylation by H3.3K36M in preadipocytes inhibits adipogenesis by increasing H3K27me3 to prevent the induction of C/EBPα and other targets of the master adipogenic transcription factor peroxisome proliferator-activated receptor-γ (PPARγ). Depleting H3K36 methyltransferase Nsd2, but not Nsd1 or Setd2, phenocopies the effects of H3.3K36M on adipogenesis and PPARγ target expression. Consistently, expression of H3.3K36M in progenitor cells impairs brown adipose tissue (BAT) and muscle development in mice. In contrast, depletion of histone H3K36 methylation by H3.3K36M in adipocytes in vivo does not affect adipose tissue weight, but leads to profound whitening of BAT and insulin resistance in white adipose tissue (WAT). These mice are resistant to high fat diet-induced WAT expansion and show severe lipodystrophy. Together, these results suggest a critical role of Nsd2-mediated H3K36 methylation in adipose tissue development and function. The epigenetic mechanisms regulating adipose tissue development are poorly understood. Here the authors show that reduction of H3K36 methylation in preadipocytes, both by H3.3K36M expression and depletion of H3K36 methyltransferase Nsd2, impairs adipogenesis by increasing H3K27me3.

• Publication year

  2018

• Venue

  Nature Communications

• Publication date

  2018-05-04

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1038/s41467-018-04127-6PMID 29728617PMCID 5935725
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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