Methamphetamine (MA) Use Induces Specific Changes in LINE-1 Partial Methylation Patterns, Which Are Associated with MA-Induced Paranoia: a Multivariate and Neuronal Network Study

2018 ◽  
Vol 56 (6) ◽  
pp. 4258-4272 ◽  
Author(s):  
Rasmon Kalayasiri ◽  
Korakot Kraijak ◽  
Michael Maes ◽  
Apiwat Mutirangura
2019 ◽  
Vol 18 ◽  
pp. 117693511988051
Author(s):  
Lillian Sun ◽  
Surya Namboodiri ◽  
Emily Chen ◽  
Shuying Sun

DNA methylation plays a significant role in regulating the expression of certain genes in both cancerous and normal breast tissues. It is therefore important to study within-sample co-methylation, ie, methylation patterns between consecutive sites in a chromosome. In this article, we develop 2 new methods to compare co-methylation patterns between normal and cancerous breast samples. In particular, we investigate the co-methylation patterns of 4 different methylation states/levels separately. Using these 2 methods, we focus on addressing the following questions: How often does 1 methylation state change to other methylation states and how is this change dependent on chromosome distance? What co-methylation patterns do normal and cancerous breast samples have? Do genomic sites with different methylation states/levels have different co-methylation patterns? Our results show that cancerous and normal co-methylation patterns are significantly different. We find that this difference exists even when the physical distance of 2 sites are less than 50 bases. Breast cancer cell lines tend to remain in the same methylation state more often than normal samples, especially for the no/low or high/full methylation states. We also find that the co-methylation region lengths for various methylation states (no/low, partial, and high/full methylation states) are very different. For example, the co-methylation region lengths for partial methylation regions are shorter than the unmethylated or fully methylated regions. Our research may provide a deep understanding of co-methylation patterns. These co-methylation patterns will aid in discovering and understanding new methylation events that may be related to novel biomarkers.


2018 ◽  
Author(s):  
Rasmon Kalayasiri ◽  
Korakot Kraijak ◽  
Apiwat Mutirangura ◽  
Michael Maes

AbstractBackgroundThere is evidence that schizophrenia is a neuro-immune disorder. Genes linked to intragenic LINE-1 methylation show a strong association with immune-associated disorders including psychosis. The aim of this study was to examine LINE-1 methylation patterns in paranoid schizophrenia and methamphetamine-induced paranoia, a model for schizophrenia.MethodsThis study recruited 31 patients with paranoid schizophrenia, 94 with methamphetamine-induced paranoia (MIP) and 163 normal controls. LINE-1 methylation patterns were assayed in peripheral blood mononuclear cells and a combined bisulphite restriction analysis and COBRA were used to estimate global methylation (mC) and LINE-1 CpG dinucleotide methylation patterns, namely 2 methylated (mCmC) and 2 unmethylated (uCuC) CpGs and the partially methylated loci mCuC (5’m with 3’u) and uCmC (5’u with 3’m).ResultsPatients with paranoid schizophrenia show highly significant changes in LINE-1 partial methylation patterns, namely a higher % mCuC and lower % uCmC as compared with controls and MIP patients, while the latter show higher % mCuC but lower % uCmC as compared with controls. Higher % mCuC significantly predicts paranoid schizophrenia with a sensitivity of 51.6%, specificity of 97.5% and an area under the ROC curve of 0.895.ConclusionsThe results indicate that a common dysfunction in LINE-1 partial methylation may underpin both paranoid schizophrenia and MIP and that this methylation pattern is significantly more expressed in paranoid schizophrenia than MIP. Reciprocal links between impairments in LINE-1 methylation and neuro-immune and neuro-oxidative pathways may underpin the pathophysiology of both MIP and paranoid schizophrenia.


1993 ◽  
Vol 292 (3) ◽  
pp. 701-704 ◽  
Author(s):  
M Peshavaria ◽  
I N M Day

The methylation status in the human-muscle enolase gene (ENO3) was assayed. Previous sequence data and MspI cleavage sites indicate the presence of a 5′ CpG-rich island of at least 4 kb: none of 22 characterized MspI CCGG sites is methylated in any of muscle, sperm or brain DNA. However a complex pattern of complete and partial methylation of MspI sites that is different between tissues is observed within the ENO3 gene: events at one site may be specific to muscle DNA. The absence of methylation in the promoter region of the ENO3 gene makes it unlikely that methylation plays a causal role either in transcriptional events or in the divergence of enolase-isogene regulation. The role of tissue-specific methylation events within ENO3 remains to be determined.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Ruangsak Lertkhachonsuk ◽  
Krissada Paiwattananupant ◽  
Patou Tantbirojn ◽  
Prakasit Rattanatanyong ◽  
Apiwat Mutirangura

Objective. To study the potential of long interspersed element-1 (LINE-1) methylation change in the prediction of postmolar gestational trophoblastic neoplasia (GTN).Methods. The LINE-1 methylation pattern from first trimester placenta, hydatidiform mole, and malignant trophoblast specimens were compared. Then, hydatidiform mole patients from 11999 to 2010 were classified into the following 2 groups: a remission group and a group that developed postmolar GTN. Specimens were prepared for a methylation study. The methylation levels and percentages of LINE-1 loci were evaluated for their sensitivity, specificity, and accuracy for the prediction of postmolar GTN.Results. First, 12 placentas, 38 moles, and 19 malignant trophoblast specimens were compared. The hydatidiform mole group had the highest LINE-1 methylation level (p= 0.003) and theuCuC of LINE-1 increased in the malignant trophoblast group (p≤ 0.001). One hundred forty-five hydatidiform mole patients were classified as 103 remission and 42 postmolar GTN patients. The %mCuC and %uCmC of LINE-1 showed the lowestpvalue for distinguishing between the two groups (p< 0.001). The combination of the pretreatmentβ-hCG level (≥100,000 mIU/mL) with the %mCuC and %uCmC, sensitivity, specificity, PPV, NPV, and accuracy modified the levels to 60.0%, 92.2%, 77.4%, 83.8%, and 82.3%, respectively.Conclusions. A reduction in the partial methylation of LINE-1 occurs early before the clinical appearance of malignant transformation. The %mCuC and %uCmC of LINE-1s may be promising markers for monitoring hydatidiform moles before progression to GTN.


Nature ◽  
2017 ◽  
Vol 546 (7660) ◽  
pp. 579-579
Keyword(s):  

2020 ◽  
Author(s):  
Avital Perry ◽  
Christopher S. Graffeo ◽  
Lucas P. Carlstrom ◽  
Amanda Munoz Casabella ◽  
Matthew L. Carlson ◽  
...  

2008 ◽  
Vol 39 (01) ◽  
Author(s):  
F Otto ◽  
J Opatz ◽  
R Hartmann ◽  
D Willbold ◽  
E Donauer ◽  
...  

2007 ◽  
Vol 30 (4) ◽  
pp. 90
Author(s):  
Kirsten Niles ◽  
Sophie La Salle ◽  
Christopher Oakes ◽  
Jacquetta Trasler

Background: DNA methylation is an epigenetic modification involved in gene expression, genome stability, and genomic imprinting. In the male, methylation patterns are initially erased in primordial germ cells (PGCs) as they enter the gonadal ridge; methylation patterns are then acquired on CpG dinucleotides during gametogenesis. Correct pattern establishment is essential for normal spermatogenesis. To date, the characterization and timing of methylation pattern acquisition in PGCs has been described using a limited number of specific gene loci. This study aimed to describe DNA methylation pattern establishment dynamics during male gametogenesis through global methylation profiling techniques in a mouse model. Methods: Using a chromosome based approach, primers were designed for 24 regions spanning chromosome 9; intergenic, non-repeat, non-CpG island sequences were chosen for study based on previous evidence that these types of sequences are targets for testis-specific methylation events. The percent methylation was determined in each region by quantitative analysis of DNA methylation using real-time PCR (qAMP). The germ cell-specific pattern was determined by comparing methylation between spermatozoa and liver. To examine methylation in developing germ cells, spermatogonia from 2 day- and 6 day-old Oct4-GFP (green fluorescent protein) mice were isolated using fluorescence activated cell sorting. Results: As compared to liver, four loci were hypomethylated and five loci were hypermethylated in spermatozoa, supporting previous results indicating a unique methylation pattern in male germ cells. Only one region was hypomethylated and no regions were hypermethylated in day 6 spermatogonia as compared to mature spermatozoa, signifying that the bulk of DNA methylation is established prior to type A spermatogonia. The methylation in day 2 spermatogonia, germ cells that are just commencing mitosis, revealed differences of 15-20% compared to day 6 spermatogonia at five regions indicating that the most crucial phase of DNA methylation acquisition occurs prenatally. Conclusion: Together, these studies provide further evidence that germ cell methylation patterns differ from those in somatic tissues and suggest that much of methylation at intergenic sites is acquired during prenatal germ cell development. (Supported by CIHR)


Sign in / Sign up

Export Citation Format

Share Document