2022
DOI: 10.3390/ijms23179691
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Polyploidy and Myc Proto-Oncogenes Promote Stress Adaptation via Epigenetic Plasticity and Gene Regulatory Network Rewiring

Abstract: Polyploid cells demonstrate biological plasticity and stress adaptation in evolution; development; and pathologies, including cardiovascular diseases, neurodegeneration, and cancer. The nature of ploidy-related advantages is still not completely understood. Here, we summarize the literature on molecular mechanisms underlying ploidy-related adaptive features. Polyploidy can regulate gene expression via chromatin opening, reawakening ancient evolutionary programs of embryonality. Chromatin opening switches on ge… Show more

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Cited by 24 publications
(31 citation statements)
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References 222 publications
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“…Polyploidy as such (in normal mammalian tissues) induces a similar epigenetic shift favouring upregulation of unicellular and early multicellular genes (phylogenetic strata 1–5, from Prokaryotes to Eumetazoa), accompanied by downregulation of the genes of complex multicellularity, responsible for apoptosis, differentiation, immunity, and cell communication [ 72 ]. This shift towards unicellularity is aided by the ploidy-upregulated key proto-oncogene c-myc (originated in Opisthokonta) opening the chromatin for reprogramming [ 73 ], leading to epithelial-mesenchymal transition (EMT) [ 72 , 74 , 75 , 76 ] and hubbing the network nest of upregulated bivalent genes (in the same phylogenetic strata 1–5). The latter enable a critically rapid switch of the gene promoter activity from a suppressed to an active state.…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation
“…Polyploidy as such (in normal mammalian tissues) induces a similar epigenetic shift favouring upregulation of unicellular and early multicellular genes (phylogenetic strata 1–5, from Prokaryotes to Eumetazoa), accompanied by downregulation of the genes of complex multicellularity, responsible for apoptosis, differentiation, immunity, and cell communication [ 72 ]. This shift towards unicellularity is aided by the ploidy-upregulated key proto-oncogene c-myc (originated in Opisthokonta) opening the chromatin for reprogramming [ 73 ], leading to epithelial-mesenchymal transition (EMT) [ 72 , 74 , 75 , 76 ] and hubbing the network nest of upregulated bivalent genes (in the same phylogenetic strata 1–5). The latter enable a critically rapid switch of the gene promoter activity from a suppressed to an active state.…”
Section: Introductionmentioning
confidence: 99%
“…The latter enable a critically rapid switch of the gene promoter activity from a suppressed to an active state. Moreover, cancer gene ontology (GO) modules embracing the c-MYC-HRAS axis and EGFR nest become activated by polyploidy [ 72 , 74 , 75 , 76 ].…”
Section: Introductionmentioning
confidence: 99%
“…In accordance, the MCODE complex investigation found complexes implicated in RNA transport, mRNA and tRNA processing, basal transcription (regulated by Taf8, Taf2, Gtf2B and Gtf2E1), and ribosome biogenesis (regulated by Brix1, Pes1, Mak16). The activation of transcription and ribosome biogenesis may be the consequence of the transcriptionally permissive chromatin state originating from polyploidy, genetic instability, and other factors related to stress [ 79 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 ]. This suggestion is confirmed by the GO biological process “Negative regulation of chromosome organization” ( Figure 7 A).…”
Section: Resultsmentioning
confidence: 99%
“…Our data also identified the traits of open chromatin, such as the upregulation of the gene module “Negative regulation of chromosome organization” and modules related to active transcription and ribosome biogenesis. The association between polyploidy, chromatin opening, ribosome biogenesis, and active transcription was previously described in several studies performed with mammalian and plant cells in normal and pathologic states [ 91 , 145 , 146 , 147 ].…”
Section: Discussionmentioning
confidence: 99%
“…Polyploidization makes cancer cells even worse because of chromosomal instability caused by difficulties with chromosome pairing and segregation [ 58 , 59 , 60 , 61 , 63 ]. Another recently recognized factor of gene expression changes in polyploid cells is the opening of chromatin owing to a decrease in surface/volume ratio, which relaxes chromatin architecture because of the loss of interactions of nuclear lamina with lamina-associated domains [ 90 ]. Chromatin opening may also cause cell dedifferentiation.…”
Section: Discussionmentioning
confidence: 99%