scholarly journals DNA methylation and gene expression patterns in adipose tissue differ significantly within young adult monozygotic BMI-discordant twin pairs

2015 ◽  
Vol 40 (4) ◽  
pp. 654-661 ◽  
Author(s):  
K H Pietiläinen ◽  
K Ismail ◽  
E Järvinen ◽  
S Heinonen ◽  
M Tummers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
Young Adult ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Discordant Twin

scholarly journals Gene expression profiling of epigenetic chromatin modification enzymes and histone marks by cigarette smoke: implications for COPD and lung cancer

2016 ◽  
Vol 311 (6) ◽  
pp. L1245-L1258 ◽  
Author(s):  
Isaac K. Sundar ◽  
Irfan Rahman
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Dna Methylation ◽  
Cigarette Smoke ◽  
Histone Modifications ◽  
Expression Patterns ◽  
Chromatin Modification ◽  
Gene Expression Patterns ◽  
Validation Data ◽  
Histone Marks

Chromatin-modifying enzymes mediate DNA methylation and histone modifications on recruitment to specific target gene loci in response to various stimuli. The key enzymes that regulate chromatin accessibility for maintenance of modifications in DNA and histones, and for modulation of gene expression patterns in response to cigarette smoke (CS), are not known. We hypothesize that CS exposure alters the gene expression patterns of chromatin-modifying enzymes, which then affects multiple downstream pathways involved in the response to CS. We have, therefore, analyzed chromatin-modifying enzyme profiles and validated by quantitative real-time PCR (qPCR). We also performed immunoblot analysis of targeted histone marks in C57BL/6J mice exposed to acute and subchronic CS, and of lungs from nonsmokers, smokers, and patients with chronic obstructive pulmonary disease (COPD). We found a significant increase in expression of several chromatin modification enzymes, including DNA methyltransferases, histone acetyltransferases, histone methyltransferases, and SET domain proteins, histone kinases, and ubiquitinases. Our qPCR validation data revealed a significant downregulation of Dnmt1, Dnmt3a, Dnmt3b, Hdac2, Hdac4, Hat1, Prmt1, and Aurkb. We identified targeted chromatin histone marks (H3K56ac and H4K12ac), which are induced by CS. Thus CS-induced genotoxic stress differentially affects the expression of epigenetic modulators that regulate transcription of target genes via DNA methylation and site-specific histone modifications. This may have implications in devising epigenetic-based therapies for COPD and lung cancer.

scholarly journals Reversal of ageing- and injury-induced vision loss by Tet-dependent epigenetic reprogramming

2019 ◽  
Author(s):  
Yuancheng Lu ◽  
Anitha Krishnan ◽  
Benedikt Brommer ◽  
Xiao Tian ◽  
Margarita Meer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Expression Patterns ◽  
The Body ◽  
Gene Expression Patterns ◽  
Nerve Crush ◽  
Dna Methylation Age ◽  
Methylation Patterns

Ageing is a degenerative process leading to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise, which disrupts youthful gene expression patterns that are required for cells to function optimally and recover from damage1–3. Changes to DNA methylation patterns over time form the basis of an ‘ageing clock’4, 5, but whether old individuals retain information to reset the clock and, if so, whether this would improve tissue function is not known. Of all the tissues in the body, the central nervous system (CNS) is one of the first to lose regenerative capacity6, 7. Using the eye as a model tissue, we show that expression of Oct4, Sox2, and Klf4 genes (OSK) in mice resets youthful gene expression patterns and the DNA methylation age of retinal ganglion cells, promotes axon regeneration after optic nerve crush injury, and restores vision in a mouse model of glaucoma and in normal old mice. This process, which we call recovery of information via epigenetic reprogramming or REVIVER, requires the DNA demethylases Tet1 and Tet2, indicating that DNA methylation patterns don’t just indicate age, they participate in ageing. Thus, old tissues retain a faithful record of youthful epigenetic information that can be accessed for functional age reversal.

scholarly journals The effects of 30 days resveratrol supplementation on adipose tissue morphology and gene expression patterns in obese men

2013 ◽  
Vol 38 (3) ◽  
pp. 470-473 ◽  
Author(s):  
E Konings ◽  
S Timmers ◽  
M V Boekschoten ◽  
G H Goossens ◽  
J W Jocken ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Tissue Morphology

scholarly journals 26ABERRANT REPROGRAMMING OF IMPRINTED GENE EXPRESSION IN ENLARGED PLACENTAS OF MICE CLONED FROM ES CELLS TREATED WITH TSA OR 5AZAC

2004 ◽  
Vol 16 (2) ◽  
pp. 135
Author(s):  
S.G. Baqir ◽  
Q. Zhou ◽  
A. Jouneau ◽  
J.-P. Renard ◽  
D.H. Betts ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Histone Acetylation ◽  
Nuclear Transfer ◽  
Es Cells ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Imprinted Genes ◽  
Imprinted Gene ◽  
Donor Cells

The success rate of producing cloned animals is very low, and in many cases is associated with the formation of enlarged placentas. Increasing evidence has pointed towards epigenetic deregulation of imprinted genes due to incomplete or abnormal resetting of DNA methylation and/or histone acetylation patterns during development. It has previously been shown that drugs that alter DNA methylation (5AzaC) and histone acetylation (TSA) over-express imprinted genes in mouse ES cells (Baqir and Smith, 2001, Theriogenology 55, 410). Our objective in this study was to determine whether nuclear transfer is able to reprogram imprinted gene expression patterns in the placenta of mice cloned from ES donor nuclei exposed to 5AzaC and TSA. ES donor cells were treated with either TSA or 5AzaC prior to injection into enucleated oocytes. Total RNA was extracted from placentas of day 14–15 fetus clones, and reversed transcribed; the expression pattern of imprinted genes (Ipl, Mash2, Igf2, H19, Igf2r, p57, Peg1), non-imprinted placental-specific genes (Esx1, Dlx3, Tpbp) and a housekeeping gene (Gapdh) was examined by Real Time PCR. Samples were standardized with an exogenous control (Globin) and expressed as fold changes in relation to placentas of cloned fetus derived from non-treated donor cells. Data were analyzed by ANOVA and mean gene expression values were compared using the Tukey-Kramer test. Our results show that several imprinted genes (Mash2, H19, Ipl) and placenta-specific genes (Esx1 and Dlx1) were properly reprogrammed in non-enlarged (71mg) placentas of fetus clones derived from the TSA and 5AzaC treated ES donor cells. Although Gapdh expression did not differ among normal and enlarged 210mg) placenta groups, the expression level of Igf2 and Mash2 was higher in enlarged placentas from fetus clones produced from TSA-treated ES donor cells (4.6 and 3.5 fold) compared to non-enlarged placentas from non-treated ES cells (1 fold). Conversely, oversized placentas from cloned fetuses derived from TSA-treated donor ES cells under-expressed Peg1, H19 and Ipl (0.5, 0.2 and 0.2 fold, respectively) compared to control placentas (1 fold). In addition, enlarged placentas from the TSA- and 5AzaC-treated group displayed down-regulation of placenta specific genes Esx1 and Dlx3 and up-regulation of Tpbp, suggesting the presence of abnormal distribution of placental layers. These results indicate that while several imprinted and non-imprinted placenta specific genes were correctly expressed in normal size placentas of fetus clones derived from TSA and 5AzaC treated donor ES cells, enlarged placentas displayed aberrant gene expression patterns, suggesting that improper resetting of the epigenetic program after nuclear transfer is directly related to altered DNA methylation and histone acetylation patterns. Funded by NSERC & CIHR.

scholarly journals DNA Methylation Patterning and the Regulation of Beta Cell Homeostasis

2021 ◽  
Vol 12 ◽  
Author(s):  
Nazia Parveen ◽  
Sangeeta Dhawan
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Beta Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Expression Patterns ◽  
Cell Phenotype ◽  
Gene Expression Patterns ◽  
Postnatal Life ◽  
Methylation Patterns

Pancreatic beta cells play a central role in regulating glucose homeostasis by secreting the hormone insulin. Failure of beta cells due to reduced function and mass and the resulting insulin insufficiency can drive the dysregulation of glycemic control, causing diabetes. Epigenetic regulation by DNA methylation is central to shaping the gene expression patterns that define the fully functional beta cell phenotype and regulate beta cell growth. Establishment of stage-specific DNA methylation guides beta cell differentiation during fetal development, while faithful restoration of these signatures during DNA replication ensures the maintenance of beta cell identity and function in postnatal life. Lineage-specific transcription factor networks interact with methylated DNA at specific genomic regions to enhance the regulatory specificity and ensure the stability of gene expression patterns. Recent genome-wide DNA methylation profiling studies comparing islets from diabetic and non-diabetic human subjects demonstrate the perturbation of beta cell DNA methylation patterns, corresponding to the dysregulation of gene expression associated with mature beta cell state in diabetes. This article will discuss the molecular underpinnings of shaping the islet DNA methylation landscape, its mechanistic role in the specification and maintenance of the functional beta cell phenotype, and its dysregulation in diabetes. We will also review recent advances in utilizing beta cell specific DNA methylation patterns for the development of biomarkers for diabetes, and targeting DNA methylation to develop translational approaches for supplementing the functional beta cell mass deficit in diabetes.

40 PIG CLONING AND GENE EXPRESSION PATTERNS IN MINIPIG ADIPOSE TISSUE-DERIVED MESENCHYMAL STEM CELLS

2013 ◽  
Vol 25 (1) ◽  
pp. 168
Author(s):  
M. J. Kim ◽  
H. J. Oh ◽  
J. E. Park ◽  
G. A. Kim ◽  
E. J. Park ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Expression Patterns ◽  
Donor Cell ◽  
Total Cell ◽  
Laboratory Animals ◽  
Gene Expression Patterns ◽  
Significant Difference

In several laboratory animals and humans, adipose tissue-derived mesenchymal stem cells (ASC) are very interesting; they are easy to harvest and can expand to generate millions of cells from a small quantity of fat. The ASC are known as useful materials for clinical applications in human cell therapy and as a donor cell in somatic cell nuclear transfer (SCNT). In this study, we investigated the expression patterns of several genes (Oct-4, Nanog, Sox2, Dnmt1, and Dnmt3b) in minipig ASC, and whether ASC can be a suitable donor cell type for producing cloned pigs. For the study, we respectively isolated ASC, adult skin fibroblast (ASF) and fetal fibroblast (FF) from a 6-year-old female minipig. The ASC were attached to a plastic dish with a fibroblast-like morphology, expressed cell-surface marker characteristics of stem cells, and underwent osteogenic, adipogenic, and neurogenic differentiation when exposed to specific differentiation-inducing conditions. To observe gene expression, total RNA was extracted from ASC, FF, and ASF, respectively, and was used for reverse transcription (RT). After RT, real-time PCR was performed to investigate the expression of Oct-4, Sox2, Nanog, Dnmt1, and Dnmt3b. The expression of β-actin was measured and used as an endogenous control. In the following experiment, we carried out SCNT using ASC, ASF, and FF. The ratio of blastocysts to 2-cell embryos and total cell number of blastocysts were monitored as experimental parameters. Statistical analysis was performed using one-way ANOVA (GraphPad Prism version 5). As a result, the relative abundance of DNMT1 in ASC (1.9 ± 0.9) was significantly higher than that in FF and ASF (0.1 ± 0.2 and 1.0 ± 0.5, respectively; P < 0.05), but no significant difference in expression of the DNMT3b gene was observed. Interestingly, the quantity of Oct-4 was significantly higher in FF and ASC than in ASF (2.8 ± 0.4 and 2.9 ± 0.5 v. 1.0 ± 0.1, respectively; P < 0.05), and Sox2 showed significantly higher expression in ASC (3.7 ± 0.5) than in ASF and FF (1.0 ± 0.1 and 1.4 ± 0.6, respectively; P < 0.05). Nanog expression was similar in ASF, FF, and ASC. After SCNT, the developmental competence to blastocysts did not differ among the 3 groups (ASF: 7.0 ± 0.2%, FF: 16.15 ± 6.1%, and ASC: 11.1 ± 0.7%). However, total cell numbers of blastocysts derived from ASC and FF were significantly higher in ASF (89.0 ± 7.9 and 105.0 ± 5.5 v. 57.5 ± 5.2, respectively). In conclusion, the present study revealed that minipig ASC and minipig FF possess slightly different gene expression patterns and ASC have potential in terms of in vitro development and blastocyst formation ability similar to ASF and FF. This study was supported by IPET (no. 311011-05-1-SB010), RDA (no. PJ0089752012), RNL Bio (no. 550-20120006), Institute for Veterinary Science, and the BK21 program.

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