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Publications of the Week

HAM-TBS: High-Accuracy Methylation Measurements via Targeted Bisulfite Sequencing

By July 18, 2018No Comments

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 This week we profile a recent publication in Epigenetics and Chromatin from
Dr. Nadine Provencal (pictured)
at Simon Fraser University.

Can you provide a brief overview of your lab’s current research focus?

Dr. Provençal’s research group aims to understand the molecular mechanisms of how early life environmental exposures influence the development of an individual leading to disease versus health. The laboratory uses a translational approach to study the epigenetic mechanisms involved in the long-lasting effects of early life adversities and their impact on the developmental trajectories of behavioral and stress-related disorders. Epigenetic mechanisms regulate the expression of our genes without affecting the DNA sequence and can turn on or off a gene in response to environmental cues. Research in the lab combines cellular and animal models exposed to stress, where we can study in depth the mechanisms at play, as well as multiple longitudinal and cross-sectional cohorts to translate these findings to patients exposed to early life adversities. The exchange between different fields of study is essential to shed light on different aspects of the development of complex diseases and give rise to new approaches and methods to tackle the mechanisms involved. To this end, research in the lab integrates knowledge and expertise from multiple fields including epigenetics, genetics, bioinformatics, statistics and clinical research.

What is the significance of the findings in this publication?

This publication describes a novel highly accurate method to measure DNA methylation using bisulfite sequencing (termed HAM-TBS). Our ability to accurately and efficiently measure DNA methylation is critical to advance our understanding of this epigenetic mechanism and its contribution to common diseases. The presented method HAM-TBS offers a robust and low-cost method for researchers interested in DNA methylation measurements of specific target regions. In addition, we supply a validated panel to assess DNA methylation levels of important regulatory regions in the FKBP5 locus, an important gene in the regulation of the stress system and of great interest in the field of psychiatry. We developed this assay for the FKBP5 gene locus, an important gene in the regulation of the stress system and previously linked to stress-related disorders, but the method is applicable to any locus of interest.

What are the next steps for this research?

Using this novel method, we are currently assessing the effects of glucocorticoids, our stress hormone, on DNA methylation of the FKBP5 gene in multiple tissues and patients. This method allows us to accurately identify changes in DNA methylation induced by glucocorticoids to better understand the dynamics of these effects in real time and their implication in the long-term effects of early life stress on psychiatric diseases.

This research was funded by:

This study was funded by the BMBF grant Berlin-LCS (FKZ 01KR1301B) to Elisabeth Binder and an ERC starting grant (GxE molmech, grant 281338) within the FP7 funding scheme of the EU to Elisabeth Binder and fellowship from Canadian Institute of Health Research (CIHR) to Nadine Provencal.

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