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

Bashar M. Thejer; Partho P. Adhikary; Sarah L. Teakel; Johnny Fang; Paul A. Weston; Saliya Gurusinghe; Ayad G. Anwer; Martin Gosnell; Jalal A. Jazayeri; Marina Ludescher; Lesley-Ann Gray; Michael Pawlak; Robyn H. Wallace; Sameer D. Pant; Marie Wong; Tamas Fischer; Elizabeth J. New; Tanja N. Fehm; Hans Neubauer; Ewa M. Goldys; Jane C. Quinn; Leslie A. Weston; Michael A. Cahill

doi:10.1186/s12860-020-00268-z

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

Bashar M. Thejer, Partho P. Adhikary, Sarah L. Teakel, Johnny Fang, Paul A. Weston, Saliya Gurusinghe, Ayad G. Anwer, Martin Gosnell, Jalal A. Jazayeri, Marina Ludescher, Lesley-Ann Gray, Michael Pawlak, Robyn H. Wallace, Sameer D. Pant, Marie Wong, Tamas Fischer, Elizabeth J. New, Tanja N. Fehm, Hans Neubauer, Ewa M. GoldysJane C. Quinn, Leslie A. Weston, Michael A. Cahill^*

^*Corresponding author for this work

ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP)

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

30 Downloads (Pure)

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.

Original language	English
Article number	26
Pages (from-to)	1-19
Number of pages	19
Journal	BMC Molecular and Cell Biology
Volume	21
Issue number	1
DOIs	https://doi.org/10.1186/s12860-020-00268-z
Publication status	Published - 15 Apr 2020

Bibliographical note

Copyright © 2020 The Author(s). Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

Cell death
Cytochrome P450
Embryology
Epigenetics
Genomic sequence
Hyperspectral autofluorescence
Metabolism
Organizer
Steroid biology

Access to Document

10.1186/s12860-020-00268-zLicence: CC BY

Publisher version (open access)Final published version, 1.99 MBLicence: CC BY

Cite this

Thejer, B. M., Adhikary, P. P., Teakel, S. L., Fang, J., Weston, P. A., Gurusinghe, S., Anwer, A. G., Gosnell, M., Jazayeri, J. A., Ludescher, M., Gray, L.-A., Pawlak, M., Wallace, R. H., Pant, S. D., Wong, M., Fischer, T., New, E. J., Fehm, T. N., Neubauer, H., ... Cahill, M. A. (2020). PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease. BMC Molecular and Cell Biology, 21(1), 1-19. Article 26. https://doi.org/10.1186/s12860-020-00268-z

@article{eed894ccfad541538281022fcd6df016,

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

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.",

keywords = "Cell death, Cytochrome P450, Embryology, Epigenetics, Genomic sequence, Hyperspectral autofluorescence, Metabolism, Organizer, Steroid biology",

author = "Thejer, {Bashar M.} and Adhikary, {Partho P.} and Teakel, {Sarah L.} and Johnny Fang and Weston, {Paul A.} and Saliya Gurusinghe and Anwer, {Ayad G.} and Martin Gosnell and Jazayeri, {Jalal A.} and Marina Ludescher and Lesley-Ann Gray and Michael Pawlak and Wallace, {Robyn H.} and Pant, {Sameer D.} and Marie Wong and Tamas Fischer and New, {Elizabeth J.} and Fehm, {Tanja N.} and Hans Neubauer and Goldys, {Ewa M.} and Quinn, {Jane C.} and Weston, {Leslie A.} and Cahill, {Michael A.}",

note = "Copyright {\textcopyright} 2020 The Author(s). Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2020",

month = apr,

day = "15",

doi = "10.1186/s12860-020-00268-z",

language = "English",

volume = "21",

pages = "1--19",

journal = "BMC Molecular and Cell Biology",

issn = "2661-8850",

publisher = "Springer, Springer Nature",

number = "1",

}

Thejer, BM, Adhikary, PP, Teakel, SL, Fang, J, Weston, PA, Gurusinghe, S, Anwer, AG, Gosnell, M, Jazayeri, JA, Ludescher, M, Gray, L-A, Pawlak, M, Wallace, RH, Pant, SD, Wong, M, Fischer, T, New, EJ, Fehm, TN, Neubauer, H, Goldys, EM, Quinn, JC, Weston, LA & Cahill, MA 2020, 'PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease', BMC Molecular and Cell Biology, vol. 21, no. 1, 26, pp. 1-19. https://doi.org/10.1186/s12860-020-00268-z

TY - JOUR

T1 - PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease

AU - Thejer, Bashar M.

AU - Adhikary, Partho P.

AU - Teakel, Sarah L.

AU - Fang, Johnny

AU - Weston, Paul A.

AU - Gurusinghe, Saliya

AU - Anwer, Ayad G.

AU - Gosnell, Martin

AU - Jazayeri, Jalal A.

AU - Ludescher, Marina

AU - Gray, Lesley-Ann

AU - Pawlak, Michael

AU - Wallace, Robyn H.

AU - Pant, Sameer D.

AU - Wong, Marie

AU - Fischer, Tamas

AU - New, Elizabeth J.

AU - Fehm, Tanja N.

AU - Neubauer, Hans

AU - Goldys, Ewa M.

AU - Quinn, Jane C.

AU - Weston, Leslie A.

AU - Cahill, Michael A.

N1 - Copyright © 2020 The Author(s). Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2020/4/15

Y1 - 2020/4/15

N2 - 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.

AB - 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.

KW - Cell death

KW - Cytochrome P450

KW - Embryology

KW - Epigenetics

KW - Genomic sequence

KW - Hyperspectral autofluorescence

KW - Metabolism

KW - Organizer

KW - Steroid biology

UR - http://www.scopus.com/inward/record.url?scp=85083355002&partnerID=8YFLogxK

UR - http://purl.org/au-research/grants/arc/CE140100003

U2 - 10.1186/s12860-020-00268-z

DO - 10.1186/s12860-020-00268-z

M3 - Article

C2 - 32293262

AN - SCOPUS:85083355002

SN - 2661-8850

VL - 21

SP - 1

EP - 19

JO - BMC Molecular and Cell Biology

JF - BMC Molecular and Cell Biology

IS - 1

M1 - 26

ER -

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

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Cite this