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 vertebra...
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| Format: | Article |
| Language: | English |
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BMC
2020-04-01
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| Series: | BMC Molecular and Cell Biology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12860-020-00268-z |
| _version_ | 1818158956581748736 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Bashar M. Thejer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T15:38:20Z |
| format | Article |
| id | doaj.art-d57b2568cb0049e990fdf5278618e4ac |
| institution | Directory Open Access Journal |
| issn | 2661-8850 |
| language | English |
| last_indexed | 2024-12-11T15:38:20Z |
| publishDate | 2020-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Molecular and Cell Biology |
| spelling | doaj.art-d57b2568cb0049e990fdf5278618e4ac2022-12-22T00:59:52ZengBMCBMC Molecular and Cell Biology2661-88502020-04-0121111910.1186/s12860-020-00268-zPGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and diseaseBashar M. Thejer0Partho P. Adhikary1Sarah L. Teakel2Johnny Fang3Paul A. Weston4Saliya Gurusinghe5Ayad G. Anwer6Martin Gosnell7Jalal A. Jazayeri8Marina Ludescher9Lesley-Ann Gray10Michael Pawlak11Robyn H. Wallace12Sameer D. Pant13Marie Wong14Tamas Fischer15Elizabeth J. New16Tanja N. Fehm17Hans Neubauer18Ewa M. Goldys19Jane C. Quinn20Leslie A. Weston21Michael A. Cahill22School of Biomedical Sciences, Charles Sturt UniversitySchool of Biomedical Sciences, Charles Sturt UniversitySchool of Biomedical Sciences, Charles Sturt UniversitySchool of Biomedical Sciences, Charles Sturt UniversityGraham Centre for Agricultural Innovation, Charles Sturt UniversityGraham Centre for Agricultural Innovation, Charles Sturt UniversityARC Centre of Excellence for Nanoscale BioPhotonics, Macquarie UniversityARC Centre of Excellence for Nanoscale BioPhotonics, Macquarie UniversitySchool of Biomedical Sciences, Charles Sturt UniversityDepartment of Gynecology and Obstetrics, University Women’s Hospital of DusseldorfAustralian Genome Research Facility Ltd., Victorian Comprehensive Cancer CentreNMI TT Pharmaservices, Protein ProfilingSchool of Biomedical Sciences, Charles Sturt UniversitySchool of Animal and Veterinary Sciences, Charles Sturt UniversityKinghorn Centre for Clinical Genomics, Garvan Institute of Medical ResearchACRF Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, The Australian National UniversityUniversity of Sydney, School of ChemistryDepartment of Gynecology and Obstetrics, University Women’s Hospital of DusseldorfDepartment of Gynecology and Obstetrics, University Women’s Hospital of DusseldorfARC Centre of Excellence for Nanoscale BioPhotonics, Macquarie UniversityGraham Centre for Agricultural Innovation, Charles Sturt UniversityGraham Centre for Agricultural Innovation, Charles Sturt UniversitySchool of Biomedical Sciences, Charles Sturt UniversityAbstract 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.http://link.springer.com/article/10.1186/s12860-020-00268-zEpigeneticsGenomic sequenceHyperspectral autofluorescenceOrganizerEmbryologyMetabolism |
| spellingShingle | 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 PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease BMC Molecular and Cell Biology Epigenetics Genomic sequence Hyperspectral autofluorescence Organizer Embryology Metabolism |
| title | PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease |
| title_full | PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease |
| title_fullStr | PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease |
| title_full_unstemmed | PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease |
| title_short | PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease |
| title_sort | pgrmc1 effects on metabolism genomic mutation and cpg methylation imply crucial roles in animal biology and disease |
| topic | Epigenetics Genomic sequence Hyperspectral autofluorescence Organizer Embryology Metabolism |
| url | http://link.springer.com/article/10.1186/s12860-020-00268-z |
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