Our Epigenetics Seminar Series continues in October, when we will welcome Prof Peter Jones from the Van Andel Institute, USA.

See more details below, and keep an eye on our Epigenetics Seminar Series page for information on the rest of the series.

We’ve been delighted with the attendance for the past few months, and hope you can join us in October.

Join in the chat on Twitter on #AEpiAseminar.

The Seminars are held approximately every four weeks, on Thursdays. The time varies depending on the international location of the speaker. Attendance is available to all Australian Epigenetics Alliance members – so please join AEpiA for free, or check your membership here.

Professor Peter Jones has been Chief Scientific Officer of the Van Andel Institute (VAI) in Grand Rapids, Michigan since 2014.

Peter has helped pioneer the field of epigenetics, particularly its role in cancer, and helped develop novel cancer therapies. His laboratory discovered the effects of 5‑azacytidine on cytosine methylation and first established the link between DNA methylation, gene expression and differentiation.

Peter has published more than 300 scientific papers and received several honors, including an Outstanding Investigator Award. He and Stephen Baylin shared the Kirk Landon Award for Basic Cancer Research from the AACR in 2009 and the Medal of Honor from the American Cancer Society in 2011.

The whys and hows of DNA methylation

The origins and functions of DNA cytosine methylation remain enigmatic even after more than 50 years of intensive research. I will re-examine Bestor’s hypothesis that the original appearance of DNA methylation is linked to its ability to silence intragenomic transposable elements (TEs). Because cytosine methylation is inherently mutagenic and leads to diagnostic C-T transitions at methylated CpG sites in the germline, CpG depletion can be used as a surrogate for ancient methylation. We examined the distribution of CpG sites in the published whole genome sequences of 53 organisms. We found a strong correlation between CpG depletion and genome size which in turn is largely dependent on the quantity of TEs it contains. This finding provides evidence for an unrecognized function of DNA methylation which is to enable genome expansion. Given the importance of CpG methylation in this process, as well as in gene control in health and disease, the mechanisms for de novo methylation need to be understood in more detail. While the chemical mechanisms by which methyl groups are applied to the 5 position of the cytosine ring are well understood, this process is much more complicated in the context of chromatin particularly because nucleosomal DNA cannot be methylated by prokaryotic or eukaryotic methylases. We used the power of Cryo-EM to solve the structure of a tetrameric complex of two molecules each of human DNMT3A2 and DNMT3B3 bound to a nucleosome core particle. Unexpectedly, the catalytically inactive DNMT3B3 acts as an accessory protein for the potentially active DNMT3A2. This binding occurs through the involvement of the acidic patch on the nucleosomal histones whereas the DNMT3A2 is positioned on the linker DNA. The structure predicts that the nucleosome must be moved or remodeled for de novo methylation to occur as is predicted in several publications. Understanding the whys and hows of DNA methylation will help in understanding its multiple roles in health and disease.