Category Archives: DNA Methylation

Tet1 Enzyme Based Enrichment Method for Methylome Sequencing: TamC-Seq

Posted on March 12, 2013 by Nicole Kelesoglu

Here’s another great advance in methylome sequencing. You all know about bisulfite sequencing, the “gold standard” method. Unfortunately it’s expensive.  It also requires a lot of sample, due to DNA degradation. There are enrichment methods, like MeDIP-seq, that are relatively cheap. However, there is the drawback of CpG density bias. Excitingly, there is a new enzyme based enrichment method, called TamC-Seq that requires less sample, less money, and provides excellent coverage for genome-wide profiling. The devlopers are from the He group, University of Chicago. The paper is Liang Zhang et al. Tet-mediated covlent labelling of 5-methylctosine for its genome-wide detection and sequencing. (2013) Nature Communications, (4) 1517 So how does it work? Their protocol uses mouse Tet (Ten-eleven translocation)-1, (or … Continue reading →

Posted in Applications, DNA Methylation, Genomewide Methylation Profiling, Glycosylases, Hydroxymethylation, Methylation, New Lab Methods, Next Gen Sequencing | Tagged , , , , | Leave a comment

Introducing Aba-seq for Enzyme Based High-Res Mapping of Mammalian Hydroxymethylomes

Posted on February 22, 2013 by Nicole Kelesoglu

New England Biolabs is well known for its extensive in house research programs – churning out numerous publications every year. The role of hydroxymethylation as a possible cancer biomarker is a topic of keen interest for all Epigenetics researchers. So, NEB researchers are especially enthused about their recent publication in Cell, along with their collaborators from Emory University School of Medicine. Sun, Z. et al. High-Resolution Enzymatic Mapping of Genomic 5-Hydroxymethylcytosine in Mouse Embryonic Stem Cells. (2013) Cell Reports 3, 567-576. describes the Aba-seq method, an AbaSI enzyme based high-resolution hydroxymethylome mapping. (Open access.) In nature, AbaSI is a weapon in the arms race between bacteria and bacteriophages. Wildtype bacteriophages such as T4, are resistant to most restriction enzymes due … Continue reading →

Posted in Applications, Biomarkers, DNA Methylation, Enzymology, Genomewide Methylation Profiling, Hydroxymethylation, Methylation Sensitive Restriction Enzymes, New Lab Methods, Oncology, Stem Cells | Tagged , , , , , | Leave a comment

SMRT Sequencing Studies Methyltransferease Driven Virulence in E.coli (0104:H4)

Posted on November 26, 2012 by Nicole Kelesoglu

Microbiologists rushed to respond to the 2011 pathogenic E.coli (0104:H4) outbreak in Europe. The new strain’s DNA was sequenced within 3 days time. The trace back investigation identified an organic bean sprouts field as the source. Now, Pacific Biosciences with collaboration from New England Biolabs, reports Genome-wide mapping of methylated adenine residues in pathogenic Escherichia coli using single-molecule real-time sequencing in the journal, Nature Biotechnology (open access paper). Epigenetic analysis reveals the potential for restriction modification methyltransferase enzymes (RM MTases) to have important roles in this pathogenic phenotype. 0104:H4 phenotype virulence has been defined by its production of high levels of Shiga toxin. AND it turns out that this strain has specific MTases that can promote that production. SMRT sequencing … Continue reading →

Posted in DNA Methylation, Genomewide Methylation Profiling, Methyltransferases, Microbial Epigenetics, New Lab Methods, Next Gen Sequencing | Tagged , , , , | Leave a comment

Epigenetics and Fat — Not Just Girth

Posted on November 20, 2012 by Chris Womack

In honor of the U.S. national day of gustatory indulgence, I thought I’d write about girth and fat. EpiExperts Twitter friend Graham Burdge and colleagues at the University of Southampton in the United Kingdom just published an interesting paper exploring how the fat content of a mother rat’s diet affects the polyunsaturated fats in her offspring’s cells and plasma, as well as how that diet may accomplish that feat — apparently it involves promoter methylation of the gene Fads 2. But first, girth. My co-blogger Nicole recently tweeted a blog post from U.S. National Institutes of Health Director Francis Collins, who shared a map by the U.S. Centers for Disease Control showing how obesity has swept the country since 1985. It’s bracing, … Continue reading →

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The Easy Way to Study Microbe Methylomes… use SMRT sequencing!

Posted on November 5, 2012 by Nicole Kelesoglu

The most recent pub from the stream of research put forth by New England Biolabs scientists, is a collaboration with scientists from Pacific Biosciences™ . See this open access paper Iain A. Murray et al. The methylomes of six bacteria. (2012) Nucleic Acids Research. It demonstrates how the 3rd generation SMRT DNA sequencing system is used to explore bacterial methylomes. Many exciting discoveries about microbe epigenetic systems are sure to follow this technological advance! So why is DNA methylated in bacteria? Mainly it functions as part of restriction modification systems. But bacterial methyltransferases also take part in gene expression, host-pathogen interactions, DNA damage, and DNA repair. Microbe methylation modifications include N6-methyladenine (6-mA), N4-methylcytosine (4-mC) & 5-methylcytosine (5-mC). Single-molecule, real-time sequencing, … Continue reading →

Posted in Applications, Bioinformatics, DNA Methylation, Genomewide Methylation Profiling, Microbial Epigenetics, New Lab Methods, Next Gen Sequencing, Software | Tagged , , , , | Leave a comment

Canada Joins the International Human Epigenome Consortium – Q&A with Tomi Pastinen of Génome Québec

Posted on October 31, 2012 by Chris Womack

In an ambitious project investigating the interplay of environment, disease, and epigenetics, Canada is funneling $41 million into epigenomics research. It’s a multi-pronged effort to scrutinize a variety of tissue samples, disease states, and responses to environmental insults, so I called up Tomi Pastinen, the Canada research chair in human genetics, to learn more about the project. Here’s a lightly edited transcript of our conversation. But first, more about the project itself. It’s Canada’s entrée into the International Human Epigenome Consortium, and its announcement last week follows closely on the heels of last year’s launch of a European IHEC effort, BLUEPRINT (see our interview with the project’s Henk Stunnenberg here). While BLUEPRINT focused on blood epigenomes, which is common in … Continue reading →

Posted in Animal Models, Applications, DNA Methylation, Epigenome, Gene Regulation, Genomewide Methylation Profiling, Histone Modifications, Metabolism, Neuroscience, Next Gen Sequencing, Sodium Bisulfite Sequencing, Transcriptome | Tagged , , , , , , , , , , , , , | Leave a comment

A Better Way to Discriminate iPSCs vs ESCs

Posted on October 17, 2012 by Nicole Kelesoglu

First of all, a hearty congratulations to Dr. Shinya Yamanaka and Dr. John Gurdon for winning this year’s Nobel prize for Medicine, for their discoveries that adult cells could be transformed back to embryonic-like states. Recently, Dr. Yamanaka has publicly warned of dangerous “stem cell therapies” currently offered in various countries, without any pre-clinical testing in animals. This was an important message considering possible tragedies, both for any patients desperate for a cure, who end up sick or dead…and for the public, who might lose their trust in potential future stem cell therapies developed safely under strict scientific methods. Induced pluripotent stem cells (iPSCs) can be transformed from somatic cells, through the expression of only four transcription factors, using Kyoto … Continue reading →

Posted in Cellular Biology, DNA Methylation, Reduced representation bisulfite sequencing, Regenerative Medicine, Stem Cells | Tagged , , , | Leave a comment

The Epigenetics of Real-Life Stress and Serotonin

Posted on October 10, 2012 by Chris Womack

Sure, M.D.s often suffer a lot of pressure. But as I learned in a brief hospital job, nurses really bear the brunt of all the biological clean-up, red tape, weird hours, patient complaints, and snippy doctors’ demands. So this new study in PLoS One on stress-related epigenetic changes in shift-working female nurses really caught my attention, and seemed like a good followup that post on situational stress and epigenetics. Nurses under high stress appear to have their gene expression epigenetically regulated in a way that may decrease serotonin in the brain’s synapses. It seems a bit like the reverse of Prozac, and it bears a passing resemblance to what might happen at the beginning of depression. By interfering with serotonin … Continue reading →

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Does Epigenetics Prove Lamarck Right?

Posted on September 25, 2012 by Chris Womack

It seems like every article about epigenetics in the popular press includes a sentence about how maybe, just maybe this new finding or other proves that Jean-Baptiste Lamarck was right some 200 years ago. He famously tied “acquired traits” — characteristics an individual accumulates during its life, such as muscular arms — into a broader theory of how species evolve. The most recent version I’ve seen is in the Sept 8 New York Times opinion piece “Why Fathers Really Matter,” though it’s indirect and noncommittal, as Lamarck comparisons tend to be: Epigenetics proves that we are the products of history, public as well as private, in parts of us that are so intimately ours that few people ever imagined that … Continue reading →

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What could epigenetics reveal to us about human evolution?

Posted on September 3, 2012 by Nicole Kelesoglu

Sometimes you don’t need Indiana Jones to solve an archaeological mystery, sometimes you need a geneticist. The research article Matthias Meyer et al. A High-Coverage Genome Sequence from an Archaic Denisovan Individual. (2012) Science, proves that point. In the article the whole genome of a little girl who lived ~80,000 years ago, and belonged to an ancient human species called the Denosivans, is sequenced from a (big) tooth and a (tiny) knuckle. Listen here to an NPR interview on the subject. These results are why archaeologists have become as fired up as geneticists are, over next generation sequencing.  NGS has recently had a tremendous impact on their field, by producing valid ancient DNA results from some incredibly rare and precious … Continue reading →

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