Epigenetics @ PLOS Genetics

This post was written by PLOS Genetics Section Editors, Wendy Bickmore and John M. Greally.

Since the founding of the journal in 2005, PLOS Genetics has listed epigenetics as one of its areas of focus. The problem is that epigenetics, like beauty, is in the eye of the beholder (or, alternatively, like obscenity, you know epigenetics when you see it).

To some, epigenetics is any molecular mechanism of transcriptional regulatory and nuclear organisation. To others, epigenetics is a mechanism for memory that can be maintained through cell division, or across generations of multicellular organisms. Yet others think of epigenetics as the way that the environment conveys its influence to the cell, tissue or organism.

Some ideas about epigenetics conflict with each other. There are those who think of the malleability of epigenetic mechanisms of transcriptional regulation as a means by which interventions during your life can blunt or overcome your genetic makeup, while those invested in the idea of multigenerational memories take the position that choices made by your grandparents have doomed you to your phenotypic fate.

Attempting to impose a unique meaning for this ambiguous word is futile. The apocryphal saying has it that scientists would rather use each other’s toothbrushes than each other’s hypotheses. Instead, we have proposed that enthusiasts in our field continue to use the word, but on condition that they then go on to define what exactly they mean by ‘epigenetics’ [1].

A journal that says it is interested in receiving ‘epigenetics’ submissions should operate under the same rules. If PLOS Genetics is going to be a place where you send your epigenetics study for publication, it is only fair that the scientists who triage your carefully constructed manuscript be explicit about what epigenetics means to them.

By ‘them’, we mean ‘us’. Our role at the journal is to act as Section Editors with responsibility for epigenetics. We both consider ourselves epigenetics specialists, with distinct areas of research interests, and decades of experience between us. This experience has led us to appreciate that the field of epigenetics is fast-moving, diverse and exciting. We have therefore decided to open up our musings to our colleagues so that it is clear what we are looking for in epigenetics submissions to PLOS Genetics.

First and foremost, if it is good science, it doesn’t matter what you call it. We welcome being challenged with innovative, thoughtful and rigorous manuscripts. Your editors and reviewers at PLOS Genetics are your fellow scientists, we are all invested in seeing excellent work published.

However, we also thought it worthwhile to update the suggested areas of epigenetics research on the journal’s website. We propose three broad areas where we anticipate a lot of exciting science is going to occur in the next several years.

1. Regulatory mechanisms controlling genome functions in normal development and in disease.

This uses the definition that equates epigenetics with the molecular regulators of transcription and nuclear function, and applies it to questions of development and disease. This is not restricted by organism, and can encompass how extrinsic, environmental effects are mediated. While simple, descriptive association studies in human subjects are described as epigenetic and have provided intriguing preliminary findings, we suggest that it is now an appropriate time to move to the definitive studies that conclusively test such preliminary associations.

2. The interaction of DNA sequence variability with genome regulation.

We anticipate that this is going to surprise colleagues. To many people, the essence of epigenetics is that it is independent of DNA sequence variation. However, we note that variability of epigenomic assays (DNA methylation, chromatin states, transcriptional consequences etc) is increasingly recognised to be strongly influenced by DNA sequence variation. In the field of epigenetics, this is often treated as an unwanted source of noise, but we have colleagues who are identifying functional variants in the genome who have the opposite point of view, and are using epigenomic assays to reveal the non-coding DNA sequences that influence cellular function and organismal phenotypes. We therefore encourage submission of studies that embrace all of the sources of variation influencing epigenomic assays, and generating insights into the mechanisms of phenotypes.

3. The molecular and cellular mechanisms mediating the memory of past events.

Finally, we return to the mainstream definition of epigenetics that equates it with a mechanism of memory of past events. As well as purely biochemical mechanisms, we acknowledge that cell fate decisions and the composition of cell subtypes in a tissue can confer a memory of past events, a very Waddingtonian model that is now being resurrected in the era of single cell genomic studies.

The field of epigenetics is evolving rapidly. We are working to position the journal to avail itself of the innovation and creativity of our colleagues in epigenetics research, and expect the field will continue to be dynamic, challenging and exciting for years to come.

Reference

1.    Greally JM. A user’s guide to the ambiguous word “epigenetics”. Nat Rev Mol Cell Biol. 2018;19: 207–208. doi:10.1038/nrm.2017.135