TY - JOUR T1 - Genomic loci mispositioning in <em>Tmem120a</em> knockout mice yields latent lipodystrophy JF - bioRxiv DO - 10.1101/2021.04.12.439495 SP - 2021.04.12.439495 AU - Rafal Czapiewski AU - Dzmitry G. Batrakou AU - Jose I. de las Heras AU - Roderick N. Carter AU - Aishwarya Sivakumar AU - Magdalena Sliwinska AU - Charles R. Dixon AU - Shaun Webb AU - Giovanna Lattanzi AU - Nicholas M. Morton AU - Eric C. Schirmer Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/04/12/2021.04.12.439495.abstract N2 - Little is known about the proteins that direct the highly conserved patterns of spatial genome organisation in fat. Here we report that adipocyte-specific knockout of the gene encoding nuclear envelope protein Tmem120a disrupts fat genome organisation, thus causing a novel 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 manifests upon exposure to an obesogenic diet. Interestingly, similar genome organisation defects occurred in cells from FPLD2 patients that harbour nuclear envelope protein laminA mutations. Our data suggest TMEM120A may mediate/instigate novel categories of adipose tissue dysfunction across the adiposity spectrum and provide a new miRNA-based mechanism possibly driving the unexplained muscle hypertrophy in human lipodystrophy.Competing Interest StatementThe authors have declared no competing interest. ER -