scholarly journals Massively parallel bisulphite pyrosequencing reveals the molecular complexity of breast cancer-associated cytosine-methylation patterns obtained from tissue and serum DNA

2007 ◽  
Vol 18 (1) ◽  
pp. 19-29 ◽  
Author(s):  
Y. Korshunova ◽  
R. K. Maloney ◽  
N. Lakey ◽  
R. W. Citek ◽  
B. Bacher ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cytosine Methylation ◽  
Massively Parallel ◽  
Serum Dna ◽  
Molecular Complexity ◽  
Methylation Patterns

scholarly journals Methylation patterns in serum DNA for early identification of disseminated breast cancer

2017 ◽  
Vol 9 (1) ◽  
Author(s):  
Martin Widschwendter ◽  
Iona Evans ◽  
Allison Jones ◽  
Shohreh Ghazali ◽  
Daniel Reisel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Identification ◽  
Serum Dna ◽  
Methylation Patterns

Clinical significance of Stratifin, ERα and PR promoter methylation in tumor and serum DNA in Indian breast cancer patients

2010 ◽  
Vol 43 (4-5) ◽  
pp. 380-386 ◽  
Author(s):  
Sameer Mirza ◽  
Gayatri Sharma ◽  
Rajinder Parshad ◽  
Anurag Srivastava ◽  
Siddartha Datta Gupta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Significance ◽  
Promoter Methylation ◽  
Breast Cancer Patients ◽  
Serum Dna

scholarly journals Structural insights into CpG-specific DNA methylation by human DNA methyltransferase 3B

2020 ◽  
Vol 48 (7) ◽  
pp. 3949-3961 ◽  
Author(s):  
Chien-Chu Lin ◽  
Yi-Ping Chen ◽  
Wei-Zen Yang ◽  
James C K Shen ◽  
Hanna S Yuan
Keyword(s):  
Dna Methylation ◽  
Dna Methyltransferase ◽  
Cytosine Methylation ◽  
Catalytic Domain ◽  
De Novo ◽  
Water Channel ◽  
Dna Methyltransferases ◽  
Structural Basis ◽  
Cpg Sites ◽  
Methylation Patterns

Abstract DNA methyltransferases are primary enzymes for cytosine methylation at CpG sites of epigenetic gene regulation in mammals. De novo methyltransferases DNMT3A and DNMT3B create DNA methylation patterns during development, but how they differentially implement genomic DNA methylation patterns is poorly understood. Here, we report crystal structures of the catalytic domain of human DNMT3B–3L complex, noncovalently bound with and without DNA of different sequences. Human DNMT3B uses two flexible loops to enclose DNA and employs its catalytic loop to flip out the cytosine base. As opposed to DNMT3A, DNMT3B specifically recognizes DNA with CpGpG sites via residues Asn779 and Lys777 in its more stable and well-ordered target recognition domain loop to facilitate processive methylation of tandemly repeated CpG sites. We also identify a proton wire water channel for the final deprotonation step, revealing the complete working mechanism for cytosine methylation by DNMT3B and providing the structural basis for DNMT3B mutation-induced hypomethylation in immunodeficiency, centromere instability and facial anomalies syndrome.

scholarly journals Stochastic Modeling Reveals Kinetic Heterogeneity in Post-replication DNA Methylation

2019 ◽  
Author(s):  
Luis Busto-Moner ◽  
Julien Morival ◽  
Arjang Fahim ◽  
Zachary Reitz ◽  
Timothy L. Downing ◽  
...  
Keyword(s):  
Mathematical Modeling ◽  
Dna Methylation ◽  
Rate Constants ◽  
Cytosine Methylation ◽  
Temporal Dynamics ◽  
Epigenetic Modification ◽  
Embryonic Stem ◽  
Likelihood Estimation ◽  
Dna Methyltransferases ◽  
Methylation Patterns

AbstractDNA methylation is a heritable epigenetic modification that plays an essential role in mammalian development. Genomic methylation patterns are dynamically maintained, with DNA methyltransferases mediating inheritance of methyl marks onto nascent DNA over cycles of replication. A recently developed experimental technique employing immunoprecipitation of bromodeoxyuridine labeled nascent DNA followed by bisulfite sequencing (Repli-BS) measures post-replication temporal evolution of cytosine methylation, thus enabling genome-wide monitoring of methylation maintenance. In this work, we combine statistical analysis and stochastic mathematical modeling to analyze Repli-BS data from human embryonic stem cells. We estimate site-specific kinetic rate constants for the restoration of methyl marks on >10 million uniquely mapped cytosines within the CpG (cytosine-phosphate-guanine) dinucleotide context across the genome using Maximum Likelihood Estimation. We find that post-replication remethylation rate constants span approximately two orders of magnitude, with half-lives of per-site recovery of steady-state methylation levels ranging from shorter than ten minutes to five hours and longer. Furthermore, we find that kinetic constants of maintenance methylation are correlated among neighboring CpG sites. Stochastic mathematical modeling provides insight to the biological mechanisms underlying the inference results, suggesting that enzyme processivity and/or collaboration can produce the observed kinetic correlations. Our combined statistical/mathematical modeling approach expands the utility of genomic datasets and disentangles heterogeneity in methylation patterns arising from replication-associated temporal dynamics versus stable cell-to-cell differences.

scholarly journals Long-range massively parallel mate pair sequencing detects distinct mutations and similar patterns of structural mutability in two breast cancer cell lines

2011 ◽  
Vol 204 (8) ◽  
pp. 447-457 ◽  
Author(s):  
Oliver A. Hampton ◽  
Christopher A. Miller ◽  
Maxim Koriabine ◽  
Jian Li ◽  
Petra Den Hollander ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Long Range ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Massively Parallel ◽  
Breast Cancer Cell Lines ◽  
Mate Pair
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