As the march 14th issue of Cell celebrates the dynamic nucleus, there could not have been a better time to attend this “epic-genetics” conference (as described by Dr. Gerd Blobel) at Harvard Medical School (HMS). This inaugural conference hosted by BioMed Central along with its journal Epigenetics and Chromatin celebrates the anticipated merger between Epigenetics and Chromatin biochemistry. The welcome speech by Dr. Steven Henikoff made it clear that this meeting’s objective was to “get under the hood” rather than to convince anyone of the importance of these fields, as the latter part was not necessary anymore at this point of time. The organizers did a wonderful job of selecting ten broad topics to be discussed during the meeting. As the title suggests, each of these topics were addressed with special emphasis on the interactions and processes involved by pioneers in those respective fields.
Chromatin Assembly and Disassembly
Dr. Jessica Tyler, MD Anderson Cancer Center, Houston
Dr. Jessica Tyler initiated this session by asking which all genes get histones when the histones are in limited supply (as is the case in ageing cells). She went on to describe that the observed reduction (about 60 percent) in nucleosome occupancy, global loss of 70% of histones and the “fuzzier” positioning of nucleosomes was a common theme in ageing. She concluded her talk by challenging the current paradigm of gene expression profiles in the context of ageing by postulating that, instead of a few genes being up or down regulated may be all of the genes are being induced during ageing by this “fuzzier” nucleosome positioning and reduced histone content.
Epigenetic Editing using Tal DNA Binding Protein
Dr. Eric M Mendenhall (Broad Institute and Massachusetts General Hospital, Boston)
Having been exposed to chromatin dynamics, I have been curious about alternative strategies (apart from RNAi methods) of knocking down a gene instead of the physical deletion of the same from the genome. I found the talk by Dr. Eric M Mendenhall to be very interesting as he discussed a novel method of gene regulation by combining the specificity of transcription activator-like (TAL) effector DNA binding proteins and the power of chromatin modifying enzymes. This fusion of TAL DNA binding protein to LSD1 (lysine specific demethylase) was used to locally modify the chromatin state to study the effect of an enhancer on various downstream target genes.
Dr. Bradley Cairns, University of Utah, Salt Lake City
Dr. Cairns started his talk by discussing the similarity of epigenetic modifications in zebrafish and humans, stressing the importance of zebrafish as an ideal model organism for such studies. He pointed out that even though 95% percent of histones are removed during spermiogenesis, the 5% of remaining histones might be playing a role in guiding the development of an embryo.
The discovery of these retained nucleosomes with not just the canonical histone but also the modified ones at developmentally important genes was discussed to further strengthen this argument. He argued that the analysis of about 7300 differentially methylated regions suggests that both the pattern of hypomethylated and bivalent chromatin states found in ES cells are quite similar to that found in sperms. Dr. Cairns suggested that may be the paternal genome was instructing the maternal genome on the future configuration of DNA methylation pattern. It was also interesting to note that in case of repeat elements, this phenomenon varied among different classes of retrotransposons.
Simultaneous Measurement of Nucleosome Occupancy and DNA Methylation
Dr. Peter A Jones (University of Southern California, Los Angeles)
NOMe-seq, a novel method to map nucleosome positioning by taking advantage of a bacterial methyltransferase which methylates only GpC was used to decipher nucleosome occupancy based on enzyme accessibility. This methyltransferase-based footprinting is a highly preferable method in comparison to traditional methods to study DNA methylation and nucleosome occupancy. Since only GpC’s are methylated by the enzyme, the residual CpG methylation and the nucleosome occupancy pattern could be deciphered simultaneously using bioinformatics analysis of the sequenced template.
Dr. Jones clarified that even though this method might miss out on two or more consecutive clusters of CpG’s which would produce a GpC, the advantages of this method overweighs such infrequent errors. Since gene expression would be a function of both of these parameters, a method to decipher both DNA methylation and nucleosome occupancy simultaneously could lead to new ways to understand the relationship of mutations on chromatin remodeling enzymes and disease.
Charting the Regulatory Landscape of the Mouse Genome in vivo:
Dr. Orsolya Symmons, European Molecular Biology Laboratory, Germany
The session on chromatin interactions could not have started with a better introduction than that given by Dr. Job Dekker (pioneer of the 3C method). In this session a talk that intrigued me the most was the study of regulatory landscapes in vivo to study the effect of genomic context on gene expression. A lac Z reporter gene was targeted to various locations using a controlled mobilization of a transposon (sleeping beauty). The new technique GROMIT (Genome Regulatory Organization Mapping with Integrated Transposons) helps to study the effect of genomic context on gene expression in vivo. Since the large collection of insertions (about 1000) generated by this study enticed Dr. Job Dekker to immediately forge a collaboration (even before the questioning session was over), I believe this is definitely one of the many interesting stories that was told at this conference.
Big thanks to Arun Kannanganat for providing us great overage of this event. Any additional questions for Arun can be directed to firstname.lastname@example.org.