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

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

20 Citations (Scopus)

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
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

Access to Document

10.1186/s12860-020-00268-z

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), Article 26. https://doi.org/10.1186/s12860-020-00268-z

@article{899ad33251be4ac6b6e157b8d6fee81c,

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 Gray, {Lesley Ann} 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 = "Publisher Copyright: {\textcopyright} 2020 The Author(s).",

year = "2020",

month = apr,

day = "15",

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

language = "English",

volume = "21",

journal = "BMC Molecular and Cell Biology",

issn = "2661-8850",

publisher = "BioMed Central (BMC)",

number = "1",

}

Thejer, BM, Adhikary, PP, Teakel, SL, Fang, J, Weston, PA, Gurusinghe, S, Anwer, AG, Gosnell, M, Jazayeri, JA, Ludescher, M, Gray, LA, 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. 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.

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

U2 - 10.1186/s12860-020-00268-z

DO - 10.1186/s12860-020-00268-z

M3 - Article

SN - 2661-8850

VL - 21

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

Access to Document

Other files and links

Fingerprint

Cite this