PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease

BMC Molecular and Cell Biology

Tamas Fischer¹  Ewa M. Goldys²  Martin Gosnell²  Ayad G. Anwer²  Lesley-Ann Gray³  Hans Neubauer⁴  Tanja N. Fehm⁴  Marina Ludescher⁴  Leslie A. Weston⁵  Paul A. Weston⁵  Jane C. Quinn⁵  Saliya Gurusinghe⁵  Marie Wong⁶  Michael Pawlak⁷  Sameer D. Pant⁸  Partho P. Adhikary⁹  Sarah L. Teakel⁹  Michael A. Cahill⁹  Bashar M. Thejer⁹  Jalal A. Jazayeri⁹  Johnny Fang⁹  Robyn H. Wallace⁹  Elizabeth J. New^1,10 

[1] ACRF Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, The Australian National University;ARC Centre of Excellence for Nanoscale BioPhotonics, Macquarie University;Australian Genome Research Facility Ltd., Victorian Comprehensive Cancer Centre;Department of Gynecology and Obstetrics, University Women’s Hospital of Dusseldorf;Graham Centre for Agricultural Innovation, Charles Sturt University;Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research;NMI TT Pharmaservices, Protein Profiling;School of Animal and Veterinary Sciences, Charles Sturt University;School of Biomedical Sciences, Charles Sturt University;University of Sydney, School of Chemistry;

关键词: Epigenetics;    Genomic sequence;    Hyperspectral autofluorescence;    Organizer;    Embryology;    Metabolism;   

DOI  :  10.1186/s12860-020-00268-z

来源: DOAJ

【 摘 要 】

Abstract Background Progesterone receptor membrane component 1 (PGRMC1) is often elevated in cancers, and exists in alternative states of phosphorylation. A motif centered on PGRMC1 Y180 was evolutionarily acquired concurrently with the embryological gastrulation organizer that orchestrates vertebrate tissue differentiation. Results Here, we show that mutagenic manipulation of PGRMC1 phosphorylation alters cell metabolism, genomic stability, and CpG methylation. Each of several mutants elicited distinct patterns of genomic CpG methylation. Mutation of S57A/Y180/S181A led to increased net hypermethylation, reminiscent of embryonic stem cells. Pathways enrichment analysis suggested modulation of processes related to animal cell differentiation status and tissue identity, as well as cell cycle control and ATM/ATR DNA damage repair regulation. We detected different genomic mutation rates in culture. Conclusions A companion manuscript shows that these cell states dramatically affect protein abundances, cell and mitochondrial morphology, and glycolytic metabolism. We propose that PGRMC1 phosphorylation status modulates cellular plasticity mechanisms relevant to early embryological tissue differentiation.

【 授权许可】

Unknown