Independence between pre-mRNA splicing and DNA methylation in an isogenic minigene resource

Nanan, Kyster K.; Ocheltree, Cody; Sturgill, David; Mandler, Mariana D.; Prigge, Maria F.; Varma, Garima; Oberdoerffer, Shalini

doi:10.1093/nar/gkx900

Cited by 6 publications

(5 citation statements)

References 115 publications

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“…DNA repeats and transposons require hypermethylation to maintain genomic instability and prevent transposition [76][77][78][79][80]. Interestingly, differentially methylated probes (DMPs) demonstrated a considerable enrichment in LINE, SINE and LTR transposon repeats, flanking endogenous retroviral sequences (HERVs) (Figure 6A-B).…”

Section: Echinaforce® Treatment Changes Dna Repeat Methylation and Hementioning

confidence: 99%

Standardized Echinacea purpurea extract primes an IFN specific innate immune monocyte response via JAK1-STAT1 dependent gene expression and epigenetic control of endogenous retroviral sequences

Declerck¹,

Pérez-Novo²,

Grielens³

et al. 2020

Preprint

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Background: Herbal remedies of Echinacea purpurea tinctures are widely used today to reduce common cold respiratory tract infections.Methods: A system biology approach involving genomewide transcriptome, epigenome and kinome activity profiles was applied to characterize the immunomodulatory effects of a standardized Echinacea purpurea extract Echinaforce® in THP1 monocytes.Results: Gene expression and DNA methylation analysis revealed activation of innate immunity related antiviral signaling networks, involving IFN, chemotaxis and immunometabolic pathways. Furthermore, phosphopeptide based kinome activity profiling and pharmacological inhibitor experiments with filgotinib confirm a key role for Janus Kinase (JAK)-1 dependent gene expression changes in innate immune signaling. Finally, Echinaforce® treatment induces DNA hypermethylation at intergenic CpG, long/short interspersed nuclear DNA repeat elements (LINE, SINE) or long termininal DNA repeats (LTR). This changes transcription of flanking endogenous retroviral sequences (HERVs), involved in an evolutionary conserved (epi)genomic protective response against viral infections.Conclusions: Altogether, our results suggest that Echinaforce® phytochemicals strengthen antiviral innate immunity by JAK1 responsive gene expression and epigenetic regulation of HERVs in monocytes, which supports its prophylactic use against common cold corona viruses (CoV), Severe Acute Respiratory Syndrome (SARS)-CoV, and new occurring strains such as SARS-CoV-2.

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Section: Echinaforce® Treatment Changes Dna Repeat Methylation and Hementioning

confidence: 99%

Standardized Echinacea purpurea extract primes an IFN specific innate immune monocyte response via JAK1-STAT1 dependent gene expression and epigenetic control of endogenous retroviral sequences

Declerck¹,

Pérez-Novo²,

Grielens³

et al. 2020

Preprint

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“…DNA methylation is pivotal in adaptation 1,21 , and generally correlates with exon inclusion in the genome/transcriptome 21 , though not in all cases 22 . The correlation aligns with the regulatory effects of MeCP2 and the methyl-free DNA-binding CTCF on splicing [23][24][25] .…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Control of Adaptive or Homeostatic Splicing of Alternative Exons andProlactinGene Expression During Interval-Training Activities of Pituitary Cells

Liu,

Nguyen,

Das

et al. 2024

Preprint

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Interval-training activities induce adaptive cellular changes without altering their fundamental identity, but the precise underlying molecular mechanisms are not fully understood. In this study, we demonstrate that interval-training depolarization (ITD) of pituitary cells triggers distinct adaptive or homeostatic splicing responses of alternative exons. This occurs while preserving the steady-state expression of theProlactinand other hormone genes. The nature of these splicing responses depends on the exon’s DNA methylation status, the methyl-C-binding protein MeCP2 and its associated CA-rich motif-binding hnRNP L. Interestingly, the steady expression of theProlactingene is also reliant on MeCP2, whose disruption during ITD leads to exacerbated overexpression and multi-exon aberrant splicing of the hormone gene transcripts, similar to the observed hyperprolactinemia or activity-dependent aberrant splicing in Rett Syndrome. Therefore, depending on how many times cells are stimulated, exons may exhibit different splicing responses to cell activities. During the ITD, epigenetic control is crucial for both adaptive or homeostatic splicing and the steady expression of theProlactinhormone gene. Disruption in this regulation may have significant implications for the development of progressive diseases.

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“…DNA methylation is pivotal in adaptation ( 1 , 21 ), and generally correlates with exon inclusion in the genome/transcriptome ( 21 ), though not in all cases ( 22 ). The correlation aligns with the regulatory effects of MeCP2 and the methyl-free DNA-binding CTCF on splicing ( 23–25 ).…”

Section: Introductionmentioning

confidence: 99%

Epigenetic control of adaptive or homeostatic splicing during interval-training activities

Liu,

Nguyen,

Das

et al. 2024

Nucleic Acids Research

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Interval-training activities induce adaptive cellular changes without altering their fundamental identity, but the precise underlying molecular mechanisms are not fully understood. In this study, we demonstrate that interval-training depolarization (ITD) of pituitary cells triggers distinct adaptive or homeostatic splicing responses of alternative exons. This occurs while preserving the steady-state expression of the Prolactin and other hormone genes. The nature of these splicing responses depends on the exon's DNA methylation status, the methyl-C-binding protein MeCP2 and its associated CA-rich motif-binding hnRNP L. Interestingly, the steady expression of the Prolactin gene is also reliant on MeCP2, whose disruption leads to exacerbated multi-exon aberrant splicing and overexpression of the hormone gene transcripts upon ITD, similar to the observed hyperprolactinemia or activity-dependent aberrant splicing in Rett Syndrome. Therefore, epigenetic control is crucial for both adaptive and homeostatic splicing and particularly the steady expression of the Prolactin hormone gene during ITD. Disruption in this regulation may have significant implications for the development of progressive diseases.

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Independence between pre-mRNA splicing and DNA methylation in an isogenic minigene resource

Cited by 6 publications

References 115 publications

Standardized Echinacea purpurea extract primes an IFN specific innate immune monocyte response via JAK1-STAT1 dependent gene expression and epigenetic control of endogenous retroviral sequences

Standardized Echinacea purpurea extract primes an IFN specific innate immune monocyte response via JAK1-STAT1 dependent gene expression and epigenetic control of endogenous retroviral sequences

Epigenetic Control of Adaptive or Homeostatic Splicing of Alternative Exons andProlactinGene Expression During Interval-Training Activities of Pituitary Cells

Epigenetic control of adaptive or homeostatic splicing during interval-training activities

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