DNA Methylation Profiles of Tph1A and BDNF in Gut and Brain of L. Rhamnosus-Treated Zebrafish

Cuomo, Mariella; Borrelli, Luca; Monica, Rosa Della; Coretti, Lorena; Riso, Giulia De; Durazzo, Luna D'Angelo Lancellotti di; Fioretti, Alessandro; Lembo, Francesca; Dinan, Timothy G.; Cryan, John F.; Cocozza, Sérgio; Chiariotti, Lorenzo

doi:10.3390/biom11020142

Cited by 23 publications

(11 citation statements)

References 35 publications

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“…Disentangling this phenomenon requires technical approach that may be challenging. In our previous works 13 – 17 , we demonstrated that the analysis of epiallele distribution may be considered a proxy of single cell studies, since epialleles represent the specific combination of methylated and unmethylated CpGs at single molecule levels. Therefore, evaluating the distribution of epialleles may mirror the different cellular composition in a given tissue and may identify DNA methylation differences among cells.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, DNA methylation at Fxyd1a increased during brain development and decreased during heart development in line with changes of mRNA expression levels. We have previously demonstrated that ultra-deep methylation analysis may help to unravel cell-to-cell heterogeneity in terms of DNA methylation 13 – 17 . By using a newly generated bioinformatic tool 18 , we were able to assess the quantitative and qualitative distribution of epialleles, intended as combination of methylated and unmethylated CpG sites on the same molecule.…”

Section: Introductionmentioning

confidence: 99%

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Epigenetic remodelling of Fxyd1 promoters in developing heart and brain tissues

Cuomo

Florio

Monica

et al. 2022

Sci Rep

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FXYD1 is a key protein controlling ion channel transport. FXYD1 exerts its function by regulating Na+/K+-ATPase activity, mainly in brain and cardiac tissues. Alterations of the expression level of the FXYD1 protein cause diastolic dysfunction and arrhythmias in heart and decreased neuronal dendritic tree and spine formation in brain. Moreover, FXYD1, a target of MeCP2, plays a crucial role in the pathogenesis of the Rett syndrome, a neurodevelopmental disorder. Thus, the amount of FXYD1 must be strictly controlled in a tissue specific manner and, likely, during development. Epigenetic modifications, particularly DNA methylation, represent the major candidate mechanism that may regulate Fxyd1 expression. In the present study, we performed a comprehensive DNA methylation analysis and mRNA expression level measurement of the two Fxyd1 transcripts, Fxyd1a and Fxyd1b, in brain and heart tissues during mouse development. We found that DNA methylation at Fxyd1a increased during brain development and decreased during heart development along with coherent changes in mRNA expression levels. We also applied ultra-deep methylation analysis to detect cell to cell methylation differences and to identify possible distinct methylation profile (epialleles) distribution between heart and brain and in different developmental stages. Our data indicate that the expression of Fxyd1 transcript isoforms inversely correlates with DNA methylation in developing brain and cardiac tissues suggesting the existence of a temporal-specific epigenetic program. Moreover, we identified a clear remodeling of epiallele profiles which were distinctive for single developmental stage both in brain and heart tissues.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Epigenetic remodelling of Fxyd1 promoters in developing heart and brain tissues

Cuomo

Florio

Monica

et al. 2022

Sci Rep

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“…Additionally, Cuomo et al documented that the administration of L. rhamnosus in larvae led to DNA methylation code of the Tph1A and BDNF promoter gene reconstruction in the gut and the brain of zebrafish. Accordingly, alterations in the gut microbiome may influence the host epigenetic landscape, resulting in long‐term consequences for specific gene regions 32 …”

Section: The Roles Of the Gut Microbiome In Tissue Development And Ph...mentioning

confidence: 99%

Application of zebrafish in the study of the gut microbiome

Zhong

et al. 2022

Anim Models and Exp Med

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The gut microbiome is widely acknowledged to coexist with the animal host, consisting of symbiotic and pathogenic bacteria in a dynamic balance state that produce a wide variety of signaling molecules. These bacteria colonize the intestine and perform functions the host itself cannot accomplish; in turn, they rely on the habitat provided by the host. A healthy gut microbiome plays a significant and irreplaceable role in determining the host's overall health.Zebrafish is an omnivorous freshwater fish that belongs to the small carp family. It has been widely used for research purposes on embryology and tissue regeneration, molecular genetics, reproductive biology, and toxicology given its numerous advantages, including high fecundity, short lifespan, highly annotated genome, optical

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“…We used deep amplicon bisulfite sequencing (D-ABS) data to synthesize 4-CpG low coverage datasets, starting from an in-house database of D-ABS amplicons produced in previously published studies (27,(44)(45)(46). Detailed descriptions of the employed amplicons can be found in Supplementary Table 1.…”

Section: Establishment Of MC Profiling Thresholdsmentioning

confidence: 99%

MC profiling: a novel approach to analyze DNA methylation heterogeneity from bulk bisulfite sequencing data

Riso

Sarnataro

Scala

et al. 2022

Preprint

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DNA methylation is an epigenetic mark implicated in crucial biological processes. Most of the knowledge about DNA methylation and its regulatory role is based on bulk experiments, in which DNA methylation of genomic regions is reported as average methylation, i.e. the fraction of methylated cytosines across a pool of cells. However, average methylation does not inform on how methylated cytosines are distributed in each single DNA molecule. In this study we propose Methylation Class (MC) profiling as a genome-wide approach to the study of DNA methylation heterogeneity from bulk bisulfite sequencing experiments. The proposed approach is built on the concept of MCs, i.e. groups of DNA molecules sharing the same number of methylated cytosines in a sample. The analysis of the relative abundances of MCs from sequencing reads incorporates the information on the overall average methylation, and directly informs on the methylation level of each molecule. By applying our approach to several publicly available Reduced Representation Bisulfite Sequencing (RRBS) datasets, we individuated cell-to-cell differences as the prevalent contributor to DNA methylation heterogeneity captured by MC profiles. Moreover, we individuated signatures of loci undergoing genomic imprinting and X inactivation, and highlighted differences between the two processes. When applying MC profiling to compare different conditions, we identified DNA methylation changes occurring in regions with almost constant overall average methylation. Altogether, our results indicate that MC profiling can provide useful insights on the epigenetic status and its evolution at multiple genomic regions.

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DNA Methylation Profiles of Tph1A and BDNF in Gut and Brain of L. Rhamnosus-Treated Zebrafish

Cited by 23 publications

References 35 publications

Epigenetic remodelling of Fxyd1 promoters in developing heart and brain tissues

Epigenetic remodelling of Fxyd1 promoters in developing heart and brain tissues

Application of zebrafish in the study of the gut microbiome

MC profiling: a novel approach to analyze DNA methylation heterogeneity from bulk bisulfite sequencing data

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