scholarly journals DNA methylation at a nutritionally sensitive region of the PAX8 gene is associated with thyroid volume and function in Gambian children

2021 ◽  
Vol 7 (45) ◽  
Author(s):  
Toby Candler ◽  
Noah Kessler ◽  
Chathura Gunasekara ◽  
Kate Ward ◽  
Philip James ◽  
...  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Diana Buitrago ◽  
Mireia Labrador ◽  
Juan Pablo Arcon ◽  
Rafael Lema ◽  
Oscar Flores ◽  
...  

AbstractDetermining the effect of DNA methylation on chromatin structure and function in higher organisms is challenging due to the extreme complexity of epigenetic regulation. We studied a simpler model system, budding yeast, that lacks DNA methylation machinery making it a perfect model system to study the intrinsic role of DNA methylation in chromatin structure and function. We expressed the murine DNA methyltransferases in Saccharomyces cerevisiae and analyzed the correlation between DNA methylation, nucleosome positioning, gene expression and 3D genome organization. Despite lacking the machinery for positioning and reading methylation marks, induced DNA methylation follows a conserved pattern with low methylation levels at the 5’ end of the gene increasing gradually toward the 3’ end, with concentration of methylated DNA in linkers and nucleosome free regions, and with actively expressed genes showing low and high levels of methylation at transcription start and terminating sites respectively, mimicking the patterns seen in mammals. We also see that DNA methylation increases chromatin condensation in peri-centromeric regions, decreases overall DNA flexibility, and favors the heterochromatin state. Taken together, these results demonstrate that methylation intrinsically modulates chromatin structure and function even in the absence of cellular machinery evolved to recognize and process the methylation signal.


2016 ◽  
Vol 113 (32) ◽  
pp. 9111-9116 ◽  
Author(s):  
Adam J. Bewick ◽  
Lexiang Ji ◽  
Chad E. Niederhuth ◽  
Eva-Maria Willing ◽  
Brigitte T. Hofmeister ◽  
...  

In plants, CG DNA methylation is prevalent in the transcribed regions of many constitutively expressed genes (gene body methylation; gbM), but the origin and function of gbM remain unknown. Here we report the discovery that Eutrema salsugineum has lost gbM from its genome, to our knowledge the first instance for an angiosperm. Of all known DNA methyltransferases, only CHROMOMETHYLASE 3 (CMT3) is missing from E. salsugineum. Identification of an additional angiosperm, Conringia planisiliqua, which independently lost CMT3 and gbM, supports that CMT3 is required for the establishment of gbM. Detailed analyses of gene expression, the histone variant H2A.Z, and various histone modifications in E. salsugineum and in Arabidopsis thaliana epigenetic recombinant inbred lines found no evidence in support of any role for gbM in regulating transcription or affecting the composition and modification of chromatin over evolutionary timescales.


Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 597 ◽  
Author(s):  
Patrizia D’Aquila ◽  
Laurie Lynn Carelli ◽  
Francesco De Rango ◽  
Giuseppe Passarino ◽  
Dina Bellizzi

The human gut microbiota is a complex ecosystem consisting of trillions of microorganisms that inhabit symbiotically on and in the human intestine. They carry out, through the production of a series of metabolites, many important metabolic functions that complement the activity of mammalian enzymes and play an essential role in host digestion. Interindividual variability of microbiota structure, and consequently of the expression of its genes (microbiome), was largely ascribed to the nutritional regime. Diet influences microbiota composition and function with short- and long-term effects. In spite of the vast literature, molecular mechanisms underlying these effects still remain elusive. In this review, we summarized the current evidence on the role exerted by gut microbiota and, more specifically, by its metabolites in the establishment of the host epigenome. The interest in this topic stems from the fact that, by modulating DNA methylation and histone modifications, the gut microbiota does affect the cell activities of the hosting organism.


2008 ◽  
Vol 69 (2) ◽  
pp. 345-346 ◽  
Author(s):  
G. J. Paz-Filho ◽  
C. O. Mesa ◽  
G. A. Carvalho ◽  
C. A. Goedert ◽  
H. Graf

2020 ◽  
Vol 178 (2) ◽  
pp. 325-337
Author(s):  
Matthew de Gannes ◽  
Chia-I Ko ◽  
Xiang Zhang ◽  
Jacek Biesiada ◽  
Liang Niu ◽  
...  

Abstract Congenital heart disease (CHD), the leading birth defect worldwide, has a largely unknown etiology, likely to result from complex interactions between genetic and environmental factors during heart development, at a time when the heart adapts to diverse physiological and pathophysiological conditions. Crucial among these is the regulation of cardiomyocyte development and postnatal maturation, governed by dynamic changes in DNA methylation. Previous work from our laboratory has shown that exposure to the environmental toxicant tetrachlorodibenzo-p-dioxin (TCDD) disrupts several molecular networks responsible for heart development and function. To test the hypothesis that the disruption caused by TCDD in the heart results from changes in DNA methylation and gene expression patterns of cardiomyocytes, we established a stable mouse embryonic stem cell line expressing a puromycin resistance selectable marker under control of the cardiomyocyte-specific Nkx2-5 promoter. Differentiation of these cells in the presence of puromycin induces the expression of a large suite of cardiomyocyte-specific markers. To assess the consequences of TCDD treatment on gene expression and DNA methylation in these cardiomyocytes, we subjected them to transcriptome and methylome analyses in the presence of TCDD. Unlike control cardiomyocytes maintained in vehicle, the TCDD-treated cardiomyocytes showed extensive gene expression changes, with a significant correlation between differential RNA expression and DNA methylation in 111 genes, many of which are key elements of pathways that regulate cardiovascular development and function. Our findings provide an important clue toward the elucidation of the complex interactions between genetic and epigenetic mechanisms after developmental TCDD exposure that may contribute to CHD.


2015 ◽  
Vol 112 (22) ◽  
pp. 6800-6806 ◽  
Author(s):  
Benyam Kinde ◽  
Harrison W. Gabel ◽  
Caitlin S. Gilbert ◽  
Eric C. Griffith ◽  
Michael E. Greenberg

DNA methylation at CpG dinucleotides is an important epigenetic regulator common to virtually all mammalian cell types, but recent evidence indicates that during early postnatal development neuronal genomes also accumulate uniquely high levels of two alternative forms of methylation, non-CpG methylation and hydroxymethylation. Here we discuss the distinct landscape of DNA methylation in neurons, how it is established, and how it might affect the binding and function of protein readers of DNA methylation. We review studies of one critical reader of DNA methylation in the brain, the Rett syndrome protein methyl CpG-binding protein 2 (MeCP2), and discuss how differential binding affinity of MeCP2 for non-CpG and hydroxymethylation may affect the function of this methyl-binding protein in the nervous system.


2016 ◽  
Vol 28 (11) ◽  
pp. 2786-2804 ◽  
Author(s):  
Nathan Pumplin ◽  
Alexis Sarazin ◽  
Pauline E. Jullien ◽  
Nicolas G. Bologna ◽  
Stefan Oberlin ◽  
...  
Keyword(s):  

1997 ◽  
Vol 46 (4) ◽  
pp. 493-496 ◽  
Author(s):  
B. Nygaard ◽  
J. Faber ◽  
A. Veje ◽  
J. E. M. Hansen
Keyword(s):  

2006 ◽  
Vol 91 (3) ◽  
pp. 860-864 ◽  
Author(s):  
Marta Regina Silva Alcântara ◽  
Roberto Salvatori ◽  
Paula Regina Silva Alcântara ◽  
Luciana Michele A. Nóbrega ◽  
Vera Simone Campos ◽  
...  

Abstract Objective: GH influences thyroid function and anatomy. Although goiter is frequent in acromegalic patients, the effects of GH deficiency (GHD) are difficult to assess, because hypopituitaric subjects who lack GH often also have a partial or complete deficit of TSH. Study Design: We studied thyroid morphology and serum levels of thyroid hormones in adult members of a large Brazilian kindred with untreated isolated GHD due to a homozygous mutation in the GHRH receptor gene (GHRHR; nine men and 15 women; GHD group) and compared them to subjects heterozygous for the same mutation (eight men and 10 women; HET group) and subjects homozygous for the wild-type allele [seven men and 11 women; control (CO) group]. Results: GHD subjects had a smaller thyroid volume (TV) than HET and CO. The TV of the HET group was intermediate between those of the GHD and CO groups. When TV was corrected by body surface area, it remained smaller in the GHD and HET groups than in the CO group, but the difference between GHD and HET groups disappeared. The GHD group had lower serum T3 levels than the CO group and higher free T4 levels than HET and CO groups. Conclusions: Individuals with severe untreated GHD due to a homozygous GHRHR mutation and heterozygous carriers of the same mutation have smaller TV than normal subjects, suggesting that GH has a permissive role in the growth of the thyroid gland. In addition, GHD subjects have reduced serum total T3 and increased serum free T4, suggesting a reduction in the function of the deiodinase system.


1997 ◽  
Vol 20 (3) ◽  
pp. 134-137 ◽  
Author(s):  
R. Junik ◽  
J. Sawicka ◽  
W. Kozak ◽  
M. Gembicki
Keyword(s):  

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