scholarly journals Maternal choline modifies fetal liver copper, gene expression, DNA methylation, and neonatal growth in the tx-j mouse model of Wilson disease

Epigenetics ◽  
2013 ◽  
Vol 9 (2) ◽  
pp. 286-296 ◽  
Author(s):  
Valentina Medici ◽  
Noreene M Shibata ◽  
Kusum K Kharbanda ◽  
Mohammad S Islam ◽  
Carl L Keen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Mouse Model ◽  
Wilson Disease ◽  
Fetal Liver ◽  
Liver Copper ◽  
Neonatal Growth

scholarly journals Wilson disease: intersecting DNA methylation and histone acetylation regulation of gene expression in a mouse model of hepatic copper accumulation

2021 ◽  
Author(s):  
Gaurav V. Sarode ◽  
Kari Neier ◽  
Noreene M. Shibata ◽  
Yuanjun Shen ◽  
Dmitry A Goncharov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Mouse Model ◽  
Histone Acetylation ◽  
Wilson Disease ◽  
Metabolic Pathways ◽  
Histone Deacetylases ◽  
Copper Accumulation ◽  
Copper Transporter ◽  
Pathogenic Variants

AbstractThe pathogenesis of Wilson disease (WD) is multi-factorial, involving hepatic and brain copper accumulation due to pathogenic variants affecting the ATP7B gene and downstream epigenetic and metabolic mechanisms. Prior DNA methylation investigations in human WD liver and blood and in a WD mouse model revealed an epigenetic signature of WD, including alterations in the histone deacetylase HDAC5. To test the hypothesis that histone acetylation is altered with respect to copper overload and aberrant DNA methylation in WD, we investigated class IIa histone deacetylases (HDAC4 and HDAC5) and H3K9/H3K27 histone acetylation in the Jackson Laboratory toxic milk (tx-j) mouse model of WD compared to C3HeB/FeJ (C3H) control in response to 3 treatments: 60% kcal fat diet (HFD), D-penicillamine (PCA, copper chelator), and choline (methyl group donor). HDAC5 levels significantly increased in 9-week tx-j livers after 8 days of HFD compared to chow. In 24-week tx-j livers, HDAC4/5 levels were reduced 5- to 10-fold compared to C3H likely through mechanisms involving HDAC phosphorylation. HDAC4/5 levels were also affected by disease progression and accompanied by increased acetylation. PCA and choline partially restored HDAC4, HDAC5, H3K9ac, and H3K27ac levels to that of CH3 liver. Integrated RNA and chromatin immunoprecipitation sequencing analyses revealed genes regulating energy metabolism and cellular stress/development were, in turn, regulated by histone acetylation in tx-j mice compared to C3H, with Pparα and Pparγ among the most relevant targets. These results suggest dietary modulation of class IIa HDAC4/5, and subsequent H3K9/H3K27 acetylation/deacetylation, can regulate gene expression in key metabolic pathways in the pathogenesis of WD.Significance StatementWilson disease is considered a monogenic disease caused by pathogenic variants in the ATP7B copper transporter, resulting in hepatic and brain copper accumulation. Given the lack of genotype-phenotype correlation, evidence of epigenetic and metabolic mechanisms regulating phenotype in patients and in animal models could explain the high phenotype variability observed in WD. In this study, we identify class IIa histone deacetylases as players involved in the epigenetic regulation of key metabolic pathways that can affect WD severity as well as targets sensitive to dietary modulations, which is an important characteristic for designing effective and feasible therapies. Understanding the epigenetic mechanisms in WD pathogenesis contributes to a better understanding of the phenotypic variability in WD and other common liver conditions.

scholarly journals Early Maternal Alcohol Consumption Alters Hippocampal DNA Methylation, Gene Expression and Volume in a Mouse Model

PLoS ONE ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. e0124931 ◽  
Author(s):  
Heidi Marjonen ◽  
Alejandra Sierra ◽  
Anna Nyman ◽  
Vladimir Rogojin ◽  
Olli Gröhn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Alcohol Consumption ◽  
Mouse Model ◽  
Maternal Alcohol ◽  
Maternal Alcohol Consumption

scholarly journals Developmental- and differentiation-specific patterns of human γ- and β-globin promoter DNA methylation

Blood ◽  
2007 ◽  
Vol 110 (4) ◽  
pp. 1343-1352 ◽  
Author(s):  
Rodwell Mabaera ◽  
Christine A. Richardson ◽  
Kristin Johnson ◽  
Mei Hsu ◽  
Steven Fiering ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Promoter Methylation ◽  
Fetal Liver ◽  
Globin Gene ◽  
Erythroid Cells ◽  
Promoter Dna Methylation ◽  
Globin Promoter ◽  
Promoter Dna

AbstractThe mechanisms underlying the human fetal-to-adult β-globin gene switch remain to be determined. While there is substantial experimental evidence to suggest that promoter DNA methylation is involved in this process, most data come from studies in nonhuman systems. We have evaluated human γ- and β-globin promoter methylation in primary human fetal liver (FL) and adult bone marrow (ABM) erythroid cells. Our results show that, in general, promoter methylation and gene expression are inversely related. However, CpGs at −162 of the γ promoter and −126 of the β promoter are hypomethylated in ABM and FL, respectively. We also studied γ-globin promoter methylation during in vitro differentiation of erythroid cells. The γ promoters are initially hypermethylated in CD34+ cells. The upstream γ promoter CpGs become hypomethylated during the preerythroid phase of differentiation and are then remethylated later, during erythropoiesis. The period of promoter hypomethylation correlates with transient γ-globin gene expression and may explain the previously observed fetal hemoglobin production that occurs during early adult erythropoiesis. These results provide the first comprehensive survey of developmental changes in human γ- and β-globin promoter methylation and support the hypothesis that promoter methylation plays a role in human β-globin locus gene switching.

scholarly journals Gene Expression Profiling in a Mouse Model Identifies Fetal Liver- and Placenta-Derived Potential Biomarkers for Down Syndrome Screening

PLoS ONE ◽  
2011 ◽  
Vol 6 (4) ◽  
pp. e18866 ◽  
Author(s):  
Jeroen L. A. Pennings ◽  
Wendy Rodenburg ◽  
Sandra Imholz ◽  
Maria P. H. Koster ◽  
Conny T. M. van Oostrom ◽  
...  
Keyword(s):  
Gene Expression ◽  
Down Syndrome ◽  
Mouse Model ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Fetal Liver ◽  
Potential Biomarkers ◽  
Down Syndrome Screening

scholarly journals Genome‑wide analysis of DNA methylation and gene expression changes in an ovalbumin‑induced asthma mouse model

2020 ◽  
Vol 22 (3) ◽  
pp. 1709-1716
Author(s):  
Joong‑Sun Kim ◽  
In‑Sik Shin ◽  
Na‑Rae Shin ◽  
Jae‑Yong Nam ◽  
Chul Kim
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Mouse Model ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
Asthma Mouse Model
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