Genomic loci mispositioning in Tmem120a knockout mice yields latent lipodystrophy

Rafal Czapiewski, Dzmitry G. Batrakou, Jose de las Heras, Roderick Nicholas Carter, Aishwarya Sivakumar, Magdalena Sliwinska, Charles Dixon, Shaun Webb, Giovanna Lattanzi, Nicholas M Morton, Eric C. Schirmer

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Little is known about how the observed fat-specific pattern of 3D-spatial genome organisation is established. Here we report that adipocyte-specific knockout of the gene encoding nuclear envelope transmembrane protein Tmem120a disrupts fat genome organisation, thus causing a lipodystrophy syndrome. Tmem120a deficiency broadly suppresses lipid metabolism pathway gene expression and induces myogenic gene expression by repositioning genes, enhancers and miRNA-encoding loci between the nuclear periphery and interior. Tmem120a −/− mice, particularly females, exhibit a lipodystrophy syndrome similar to human familial partial lipodystrophy FPLD2, with profound insulin resistance and metabolic defects that manifest upon exposure to an obesogenic diet. Interestingly, similar genome organisation defects occurred in cells from FPLD2 patients that harbour nuclear envelope protein encoding LMNA mutations. Our data indicate TMEM120A genome organisation functions affect many adipose functions and its loss may yield adiposity spectrum disorders, including a miRNA-based mechanism that could explain muscle hypertrophy in human lipodystrophy.

Original languageEnglish
Article number321
Number of pages18
JournalNature Communications
Issue number1
Publication statusPublished - 13 Jan 2022

Keywords / Materials (for Non-textual outputs)

  • nuclear envelope transmembrane protein (NET)
  • lipodystrophy
  • gene positioning
  • tissue specificity
  • spatial genome organisation
  • adipogenesis
  • muscle repression


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