scholarly journals Roles and Mechanisms of DNA Methylation in Vascular Aging and Related Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Hui Xu ◽  
Shuang Li ◽  
You-Shuo Liu
Keyword(s):  
Dna Methylation ◽  
Aging Process ◽  
Vascular Dysfunction ◽  
Structure And Function ◽  
Epigenetic Mechanism ◽  
Vascular Aging ◽  
Reversible Process ◽  
Therapeutic Drugs ◽  
And Function ◽  
Vascular Cell Senescence

Vascular aging is a pivotal risk factor promoting vascular dysfunction, the development and progression of vascular aging-related diseases. The structure and function of endothelial cells (ECs), vascular smooth muscle cells (VSMCs), fibroblasts, and macrophages are disrupted during the aging process, causing vascular cell senescence as well as vascular dysfunction. DNA methylation, an epigenetic mechanism, involves the alteration of gene transcription without changing the DNA sequence. It is a dynamically reversible process modulated by methyltransferases and demethyltransferases. Emerging evidence reveals that DNA methylation is implicated in the vascular aging process and plays a central role in regulating vascular aging-related diseases. In this review, we seek to clarify the mechanisms of DNA methylation in modulating ECs, VSMCs, fibroblasts, and macrophages functions and primarily focus on the connection between DNA methylation and vascular aging-related diseases. Therefore, we represent many vascular aging-related genes which are modulated by DNA methylation. Besides, we concentrate on the potential clinical application of DNA methylation to serve as a reliable diagnostic tool and DNA methylation-based therapeutic drugs for vascular aging-related diseases.

Discordant effects of guanidines on renal structure and function and on regional vascular dysfunction and collagen changes in diabetic rats

Diabetes ◽  
1997 ◽  
Vol 46 (1) ◽  
pp. 94-106 ◽  
Author(s):  
J. R. Nyengaard ◽  
K. Chang ◽  
S. Berhorst ◽  
K. M. Reiser ◽  
J. R. Williamson ◽  
...  
Keyword(s):  
Vascular Dysfunction ◽  
Diabetic Rats ◽  
Structure And Function ◽  
Renal Structure ◽  
And Function

scholarly journals Impact of DNA methylation on 3D genome structure

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Diana Buitrago ◽  
Mireia Labrador ◽  
Juan Pablo Arcon ◽  
Rafael Lema ◽  
Oscar Flores ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Chromatin Structure ◽  
Chromatin Condensation ◽  
Genome Structure ◽  
Dna Methyltransferases ◽  
Model System ◽  
Structure And Function ◽  
3D Genome ◽  
Cellular Machinery ◽  
And Function

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.

scholarly journals UNDERSTANDING AGING IN TERMS OF PHYSIOLOGICAL STATES

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S616-S617
Author(s):  
Alexander Mendenhall ◽  
Nikolay Burnaevskiy ◽  
Soo Yun ◽  
Bryan Sands
Keyword(s):  
Aging Process ◽  
Physiological State ◽  
Structure And Function ◽  
High Expression ◽  
Initial System ◽  
System Failure ◽  
C Elegans ◽  
Process Work ◽  
Acidification Capacity ◽  
And Function

Abstract The “network” of homeostatic systems fails in distinct ways in individual isogenic animals during the aging process. We believe that understanding these distinct physiological states, the transitions between them, and how they relate to homeostatic system functions will allow us to better affect change in the aging process. Work in yeast showed that fixing an initial system failure, loss of vacuole acidification capacity, could increase cellular lifespan. Here we showed how the long-lived physiological state conferred by high expression of the hsp-16.2 promoter based lifespan/penetrance biomarker correlates with differences in the expression of other genes, and the structure and function of lysosomes. We found that vacuole acidification failure is not a major initial proximal cause of aging in C. elegans – at least not in their intestine cells.

Abstract P042: Association of Epigenetic Age Acceleration and Adverse Cardiac Mechanics: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Sadiya S Khan ◽  
Tao Gao ◽  
Yinan Zheng ◽  
Laura A Colangelo ◽  
Brian Joyce ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dna Methylation ◽  
Middle Age ◽  
Cardiac Mechanics ◽  
Structure And Function ◽  
Cardiac Structure ◽  
Epigenetic Age ◽  
Epigenetic Age Acceleration ◽  
Cardiac Structure And Function ◽  
And Function

Background: Prevalence of diastolic dysfunction increases significantly with aging and becomes more prevalent in middle-age to older adulthood. DNA methylation markers of aging have been identified and integrated into an epigenetic age (EA) score, which has been demonstrated to be associated with cardiovascular morbidity and mortality. Epigenetic age acceleration (EAA) is the residual value of EA methylation markers regressed on chronologic age (CA), and is thus independent of CA. Therefore, we sought to examine the association of a previously identified DNA methylation molecular signature in blood (EAA) with cardiac mechanics. Methods: A subset of participants in the CARDIA cohort (n=1200) randomly selected (balanced on race and sex) underwent genome-wide DNA methylation profiling with the Illumina EPIC array from exam year 15 (2000-01 [age 33-45 years]) for calculation of EA and EAA. Echocardiography was completed at exam year 25 (2010-11 [age 43-55]). We used linear regression to examine the association of EA and EAA with parameters of cardiac mechanics. Models were adjusted for age, race, sex, education, study center, and Y15 cardiovascular risk factors (heart rate, body mass index, hypertension, hyperlipidemia, diabetes, and smoking). Results: Mean age of participant was 45.4±3.5 years, 52% female, and 41% black. DNA methylation markers of aging (EA and EAA) were associated with tissue Doppler measures of diastolic function, but not with parameters of left ventricular structure and systolic function ( Table ). Conclusions: EA and EAA are associated with changes in cardiac structure and function. Abnormalities in cardiac structure and function are an important intermediate phenotype prior to the development of symptomatic heart failure, and additional longitudinal research should examine DNA methylation markers as potential mediator of or novel biomarker for incident heart failure in young to middle-age adults.

Sequencing the genome and beyond

2019 ◽  
pp. 250-268
Author(s):  
Glenn-Peter Sætre ◽  
Mark Ravinet
Keyword(s):  
Dna Methylation ◽  
Candidate Genes ◽  
Evolutionary Biology ◽  
New Technologies ◽  
Structure And Function ◽  
Evolutionary Context ◽  
The Face ◽  
And Function ◽  
Near Future

Science is defined by continual progress and new technologies. This final chapter starts with introducing what it means to sequence and assemble a reference genome. It is easy to forget that the true genome is not linear but has structure and function. In this chapter the genome is explored as a 3D entity—from how it is transcribed, to how proteins interact with it, and finally to how it is actually structured. This also gives an opportunity to focus on epigenetics and how to interpret processes such as DNA methylation in an evolutionary context. The second part of the chapter focuses on ways we can interact with the genome—exploring how we might test the function and role that candidate genes play. The chapter introduces transgenics, in particular the transformative technology of CRISPR/CAS9, and explores how this might change the face of evolutionary biology in the near future.

scholarly journals DNA methylation and brain structure and function across the life course: A systematic review

2020 ◽  
Vol 113 ◽  
pp. 133-156 ◽  
Author(s):  
Emily N.W. Wheater ◽  
David Q. Stoye ◽  
Simon R. Cox ◽  
Joanna M. Wardlaw ◽  
Amanda J. Drake ◽  
...  
Keyword(s):  
Systematic Review ◽  
Dna Methylation ◽  
Life Course ◽  
Brain Structure ◽  
Structure And Function ◽  
Brain Structure And Function ◽  
And Function ◽  
The Life Course

Discordant Effects of Guanidines on Renal Structure and Function and on Regional Vascular Dysfunction and Collagen Changes in Diabetic Rats

Diabetes ◽  
1997 ◽  
Vol 46 (1) ◽  
pp. 94-106 ◽  
Author(s):  
J. R. Nyengaard ◽  
K. Chang ◽  
S. Berhorst ◽  
K. M. Reiser ◽  
J. R. Williamson ◽  
...  
Keyword(s):  
Vascular Dysfunction ◽  
Diabetic Rats ◽  
Structure And Function ◽  
Renal Structure ◽  
And Function

scholarly journals N-glycosylation profiles of the SARS-CoV-2 spike D614G mutant and its ancestral protein characterized by advanced mass spectrometry

2021 ◽  
Author(s):  
Dongxia Wang ◽  
Bin Zhou ◽  
Theodore Keppel ◽  
Maria Solano ◽  
Jakub Baudys ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Structure And Function ◽  
Wild Type ◽  
Complex Type ◽  
Total N ◽  
Therapeutic Drugs ◽  
Glycosylation Sites ◽  
And Function ◽  
Ancestral Protein ◽  
Major Target

N-glycosylation plays an important role in the structure and function of membrane and secreted proteins. The spike protein on the surface of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, is heavily glycosylated and the major target for developing vaccines, therapeutic drugs and diagnostic tests. The first major SARS-CoV-2 variant carries a D614G substitution in the spike (S-D614G) that has been associated with altered conformation, enhanced ACE2 binding, and increased infectivity and transmission. In this report, we used mass spectrometry techniques to characterize and compare the N-glycosylation of the wild type (S-614D) or variant (S-614G) SARS-CoV-2 spike glycoproteins prepared under identical conditions. The data showed that half of the N-glycosylation sequons changed their distribution of glycans in the S-614G variant. The S-614G variant showed a decrease in the relative abundance of complex-type glycans (up to 45%) and an increase in oligomannose glycans (up to 33%) on all altered sequons. These changes led to a reduction in the overall complexity of the total N-glycosylation profile. All the glycosylation sites with altered patterns were in the spike head while the glycosylation of three sites in the stalk remained unchanged between S-614G and S-614D proteins.

scholarly journals Mammalian DNA methyltransferases: new discoveries and open questions

2018 ◽  
Vol 46 (5) ◽  
pp. 1191-1202 ◽  
Author(s):  
Humaira Gowher ◽  
Albert Jeltsch
Keyword(s):  
Dna Methylation ◽  
Dna Methyltransferases ◽  
Structure And Function ◽  
Future Research ◽  
Ongoing Research ◽  
Cpg Sites ◽  
Open Questions ◽  
High Preference ◽  
And Function ◽  
Methylation Patterns

As part of the epigenetic network, DNA methylation is a major regulator of chromatin structure and function. In mammals, it mainly occurs at palindromic CpG sites, but asymmetric methylation at non-CpG sites is also observed. Three enzymes are involved in the generation and maintenance of DNA methylation patterns. DNMT1 has high preference for hemimethylated CpG sites, and DNMT3A and DNMT3B equally methylate unmethylated and hemimethylated DNA, and also introduce non-CpG methylation. Here, we review recent observations and novel insights into the structure and function of mammalian DNMTs (DNA methyltransferases), including new structures of DNMT1 and DNMT3A, data on their mechanism, regulation by post-translational modifications and on the function of DNMTs in cells. In addition, we present news findings regarding the allosteric regulation and targeting of DNMTs by chromatin modifications and chromatin proteins. In combination, the recent publications summarized here impressively illustrate the intensity of ongoing research in this field. They provide a deeper understanding of key mechanistic properties of DNMTs, but they also document still unsolved issues, which need to be addressed in future research.

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