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Thursday, August 29, 2013

Core Misconcept: Epigenetics

Sarah C.P. Williams is a science writer. She published an article in PNAS last February: Epigenetics. Here's the opening paragraphs ...
Despite the fact that every cell in a human body contains the same genetic material, not every cell looks or behaves the same. Long nerve cells stretch out the entire length of an arm or a leg; cells in the retina of the eye can sense light; immune cells patrol the body for invaders to destroy. How does each cell retain its unique properties when, in its DNA-containing nucleus, it has the same master set of genes as every other cell? The answer is in the epigenetic regulation of the genes: the control system that dictates which of many genes a cell uses and which it ignores. The same mechanism could also explain why identical twins—who have identical genes—can develop different diseases, traits, or personalities.

Epigenetic regulation consists of chemical flags, or markers, on genes that are copied along with the genes when the DNA is replicated. Without altering the sequence of DNA’s molecular building blocks, epigenetic changes can alter the way a cell interacts with DNA. These changes can block a cell’s access to a gene, turning it off for good.
Statements like that make me cringe. Not only is she ignoring decades of work on the real explanation of differential gene expression, she is also proposing an explanation that can't possibly live up to the claim she is making.

PNAS should be embarrassed.

Fortunately, I'm not the only one who was upset. Mark Ptashne had the same reaction as several hundred other scientists but he took the time to write up his objections and get them published in the April issue of PNAS [Epigenetics: Core Misconcept]. I'll quote his opening paragraph and then let you follow the link and get educated about real science.
Indeed understanding this problem has been an overarching goal of research in molecular, developmental, and, increasingly, evolutionary biology. And over the past 50 years a compelling answer has emerged from studies in a wide array of organisms. Curiously, the article ignores this body of knowledge, and substitutes for it misguided musings presented as facts.
There was a time when every molecular biology student knew how gene expression was controlled. They knew about the pioneering work in bacteria and 'phage and the exquisite details that were worked out in the '60s, '70s, and '80s. That information has been lost in recent generations. Our current crop of graduate students couldn't tell you how gene expression is controlled in bacteriophage λ.

If you are one of those students then I urge you to read Ptashne's book A Genetic Switch before it goes out of print. If the current trends continue, that information is soon going to pass out of the collective memory of molecular biologists just as it has been forgotten (or never learned) by science writers.


Anonymous said...

My dream job would be to be a science writer. People like Carl Zimmer discourage me - I can't imagine producing work as good as his. Then I hear about crap like this and I wonder whats stopping me. I wouldn't make egregious mistakes like this.

Brian said...

Thanks for drawing attention to this issue, Larry. I've been following Ptashne's pushback against the misuse of the term "epigenetic" to describe histone modifications for several years, and I've resisted the phrase "epigenetic regulation" in my own papers that describe histone modification events in gene regulation (even though others in my field have not). I also make a point of pointing out this problem when I teach about chromatin modification and the historical concept of epigenetics. Unfortunately, these types of sloppy popular science articles that overstate the role of chromatin modification in maintenance of cell identity drive what would be otherwise be more careful investigators to jump on the bandwagon in an attempt to inflate the impact of their work.

Argon said...

Ptashne's comments are spot on. The meaning of 'Epigenetics' as it is now fashionably used by many has been broadened to the point of meaninglessness. It's a shit term now, used for bafflegrab, much like 'systems biology'.

Paul C. Anagnostopoulos said...

I'd be much obliged if Brian and Argon would expand on the proper definition of epigenetics. Wiki appears to have jumped on the bandwagon:

Does it have something to do with heritability?

~~ Paul

Argon said...

Hi Paul,
Yes, Wikipedia like many other sources have jumped on the bandwagon. Note the the article mentions heritability but it's not clear that this is a clearly distinguishing criterion.

The first paragraph:
"In biology, and specifically genetics, epigenetics is the study of changes in gene expression or cellular phenotype, caused by mechanisms other than changes in the underlying DNA sequence—hence the name epi- (Greek: επί- over, above, outer) -genetics. Some of these changes have been shown to be heritable."

A later passage mentions cell differentiation as an example of epigenetic change. That's not 'heritability', it's simple differentiation. It's not necessarily DNA methylation or histone positioning (or the like) but as Ptashne notes, other mechanisms of temporal and positional regulation.

A paper by Jablonka and Lamb discusses the changing meanings of the terms here:

What I really dislike about discussions of epigenetics is the number of people who seem to have no clue that it's just 'regulation': No more special or less special than any other class of mechanisms controlling differential activity. It's just a buzz word now.

Histone methylation and the mechanisms behind the phenomenon is truly interesting scientifically. 'Epigentics' isn't: It's just a navel-gazing meta-discussion about classifying something that doesn't naturally have good boundaries. Hence the meanings change depending on who and how people look at it.

DK said...

Oh, that's right - another battle over definitions. Full of extremely important meanings and excitement.

Anonymous said...

I fear I may be one of these students -- which is yet another reason I'm so fond of your blog: you point out where my knowledge is lacking and shows me where to go to fix it. Thank you!

crf said...

And that's why the press likes the subject.

caynazzo said...

I ignore DNA methylation in the remainder of this article because its possible role in development remains unclear, and it does not exist in, for example, flies and worms—model organisms the study of which has taught us much of what we know about development.

So the author wants to talk about the COREe misconceptions of epigenetics but refuses to discuss DNA methylation, a hallmark of gene silencing in the mammalian genome? That would be like talking about the core misconceptions in Junk DNA but omitting talk of introns because Prokaryotes don't have them.

Talk about a red flag. Was this paper recommended by an academy member? I recognize at least one, Eric Davidson, in the acknowledgments.

Piotr Gąsiorowski said...

Does anyone feel like commenting on this latest gem of epigenetic studies (published online last Sunday by Nature Neuroscience)?

Brian G Dias & Kerry J Ressler, "Parental olfactory experience influences behavior and neural structure in subsequent generations"

Unknown said...

Mark Ptashne has been a member of National Academy of Sciences since 1979.