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PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease Thejer, Bashar M; Adhikary, Partho P; Teakel, Sarah L; Fang, Johnny; Weston, Paul A; Gurusinghe, Saliya; Anwer, Ayad G; Gosnell, Martin; Jazayeri, Jalal A; Ludescher, Marina; Gray, Lesley-Ann; Pawlak, Michael; Wallace, Robyn H; Pant, Sameer D; Wong, Marie; Fischer, Tamas; New, Elizabeth J; Fehm, Tanja N; Neubauer, Hans; Goldys, Ewa M; Quinn, Jane C; Weston, Leslie A; Cahill, Michael A

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.

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Title
PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease
Creator
Thejer, Bashar M; Adhikary, Partho P; Teakel, Sarah L; Fang, Johnny; Weston, Paul A; Gurusinghe, Saliya; Anwer, Ayad G; Gosnell, Martin; Jazayeri, Jalal A; Ludescher, Marina; Gray, Lesley-Ann; Pawlak, Michael; Wallace, Robyn H; Pant, Sameer D; Wong, Marie; Fischer, Tamas; New, Elizabeth J; Fehm, Tanja N; Neubauer, Hans; Goldys, Ewa M; Quinn, Jane C; Weston, Leslie A; Cahill, Michael A
Publisher
BioMed Central
Date Issued
2020-04-15
Description
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.
Subject
Epigenetics; Genomic sequence; Hyperspectral autofluorescence; Organizer; Embryology; Metabolism; Cell death; Cytochrome P450; Steroid biology
Genre
Article
Type
Text
Language
eng
Date Available
2020-04-15
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0389833
URI
http://hdl.handle.net/2429/74018
Affiliation
Pharmaceutical Sciences, Faculty of; Non UBC
Citation
BMC Molecular and Cell Biology. 2020 Apr 15;21(1):26
Publisher DOI
10.1186/s12860-020-00268-z
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
The Author(s)
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)