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

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posted on 2024-06-16, 23:09 authored by BM Thejer, PP Adhikary, SL Teakel, J Fang, PA Weston, S Gurusinghe, AG Anwer, M Gosnell, Jalal A Jazayeri, M Ludescher, LA Gray, M Pawlak, RH Wallace, SD Pant, M Wong, T Fischer, EJ New, TN Fehm, H Neubauer, EM Goldys, JC Quinn, LA Weston, MA Cahill
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.

Funding

Category 2 - Other Public Sector Grants Category

History

Volume

21

Issue

1

Start Page

1

End Page

19

Number of Pages

19

eISSN

2661-8850

ISSN

2661-8850

Publisher

Springer Science and Business Media LLC

Publisher License

CC BY

Additional Rights

CC BY 4.0

Language

en

Peer Reviewed

  • Yes

Open Access

  • Yes

Acceptance Date

2020-03-20

Era Eligible

  • Yes

Medium

Electronic

Journal

BMC Molecular and Cell Biology

Article Number

26

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