Matteo Pellegrini Talks About His Work With DNA Methylation

Emerging Research FRonts Commentary, June 2011

Matteo Pellegrini

Article: Conservation and divergence of methylation patterning in plants and animals

Authors: Feng, SH;Cokus, SJ;Zhang, XY;Chen, PY;Bostick, M;Goll, MG;Hetzel, J;Jain, J;Strauss, SH;Halpern, ME;Ukomadu, C;Sadler, KC;Pradhan, S;Pellegrini, M;Jacobsen, SE
Journal: PROC NAT ACAD SCI USA, 107 (19): 8689-8694, MAY 11, 2010
Addresses: Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA.
(Addresses have been truncated)

Matteo Pellegrini talks with and answers a few questions about this month's Emerging Research Front paper in the field of Multidisciplinary.

SW: Why do you think your paper is highly cited?

DNA methylation is known to play an important regulatory role in transcription and DNA replication. Recently it has become possible to measure the methylation state of each cytosine in a genome using next-generation sequencing of bisulfite converted DNA.

Using this approach, we were able to ask whether patterns of DNA methylation were conserved across a wide variety of organisms, from plants to animals. Our results are likely of interest to a very broad community that is interested in the organisms we profiled or more generally in epigenetics.

SW: Does it describe a new discovery, methodology, or synthesis of knowledge?

"Characterizing the role of methylation to environmental changes allows us to study the impact that diet and environmental factors have on DNA methylation."

We discovered that while certain DNA methylation patters are only found in plants (such as the methylation of non-CG sites) others are conserved across all the organisms we surveyed. In particular we found that the methylation of genes was present in all organisms. Furthermore, we showed that within genes, DNA methylation is enriched in exons compared to introns. This suggests that DNA methylation is linked with transcription in all organisms, and may serve to regulate transcript abundances as well as splicing.

SW: Would you summarize the significance of your paper in layman's terms?

Epigenetics is the study of heritable factors that influence the manner in which DNA is "read" within a cell. Current DNA sequencing technology allows us to measure epigenetic marks in an entire genome. By measuring these marks across multiple organisms, both plants and animals, we were able to show that the presence of these marks within genes is conserved in all the organisms we measured, and likely indicates that these regulatory mechanisms were present in the last common ancestor of plants and animals.

SW: How did you become involved in this research, and how would you describe the particular challenges, setbacks, and successes that you've encountered along the way?

My lab, together with the lab of Steve Jacobsen, was one of the first to develop genome-wide DNA methylation profiling approaches that detect individual bases. We developed the informatics pipeline for processing this data, which required significant changes to existing sequence alignment tools. The challenge is to integrate the methylation data with genome annotations to discover general trends, such as gene body methylation, or effects on repetitive elements. Furthermore, the applications of these data analysis pipelines to multiple genomes continue to be a complex endeavor.

SW: Where do you see your research leading in the future?

We are currently using these same genome-wide DNA methylation profiling techniques to answer fundamental questions in epigenetics. We would like to characterize how DNA methylation is inherited across generations, and to measure its plasticity in response to environmental changes. Characterizing the interaction between Mendelian genetics and epigenetic mechanisms in adaptive evolution is one of the fundamental problems of current biology. We are also extending these approaches to study variability of DNA methylation across populations to measure direct associations between methyl marks and clinically relevant phenotypes.

SW: Do you foresee any social or political implications for your research?

Characterizing the role of methylation to environmental changes allows us to study the impact that diet and environmental factors have on DNA methylation. This is of particular interest, as the environment of a pregnant mother affects not only her embryo, but the embryo's germ line and hence the mother's grandchildren. A full understanding of these effects and their underlying mechanisms could have important social consequences, affecting the behavior and reproductive health of our population.End

Matteo Pellegrini
Associate Professor
Department of Molecular, Cell and Developmental Biology
Los Angeles, CA, USA



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