A new kind of methylation

By now we're all aware of epigenetics and the role of cytosine methylation in gene expression, imprinting and retrotransposon silencing. We may however, have been fooling ourselves, since there may exist another type of methylated cytosine: 5-hydroxymethylcytosine. The journal Science will unveil 2 papers next week describing this novel modification. How could we have missed it for so long? :

"The reason that this nucleotide had not been seen before, the researchers say, is because of the methodologies used in most epigenetic experiments. Typically, scientists use a procedure called bisulfite sequencing to identify the sites of DNA methylation. But this test cannot distinguish between 5-hydroxymethylcytosine and 5-methylcytosine, a shortcoming that has kept the newly discovered nucleotide hidden for years, the researchers say. Its discovery may force investigators to revisit earlier work. The Human Epigenome Project, for example, is in the process of mapping all of the sites of methylation using bisulfite sequencing. "If it turns out in the future that (5-hydroxymethylcytosine and 5-methylcytosine) have different stable biological meanings, which we believe very likely, then epigenome mapping experiments will have to be repeated with the help of new tools that would distinguish the two," says Kriaucionis."

This is exciting, can't wait to read up on it. It seems very abundant, stable and well conserved too...

Urban dictionary for science?

Nature this week has a news feature concerning the erosion of the definitions of certain terms. It is a pet peeve of mine to hear epigenetic (it has to be heritable!) and de-differentiation (hint: if you're talking mammalian cell, you're probably wrong) misused. And I find stem cell is being used so loosely that it has sort of lost its meaning as we've discussed before.

The article tackles (excerpts to follow):

-paradigm shift:
"Unless a Nobel prize is in the offing, it might be wise for scientists to adopt the caution of contemporary historians of science and think twice before using a phrase with a complex meaning and a whiff of self promotion."

-epigenetic:
"The NIH is careful to define the epigenetics it is paying for as including both heritable and non-heritable changes in gene activity, something that Ptashne describes as "a complete joke".) Bird says he remains in favour of a relaxed usage. "Epigenetics is a useful word if you don't know what's going on — if you do, you use something else," he says."

-complexity
"Even within the precise world of binary code and bit strings, there was computational complexity, which describes how much memory and processing is required to carry out a calculation; algorithmic complexity, which is related to how much a digital description of something can be compressed; and any number of combinations and variations. "So my bottom line is, add an adjective to 'complexity'," Crutchfield says."

-race
"Race was long used to imply a shared, distinct ancestry [...] But in other contexts researchers are abandoning the term in favour of other ways to group humans, by 'population,' genetic ancestry' or 'geographic ancestry'"

-tipping point
"The term was originally coined in 1958 by sociologist Morton Grodzins in the context of studies on the racial makeup of US neighbourhoods. He found that when the migration of African-Americans into traditionally white neighbourhoods had reached a certain level, whites began to move out."

""There is no convincing theoretical argument or model that at some point the planet as a whole will snap into a second state of system," says Timothy Lenton, an Earth scientist at the University of East Anglia, UK."

-stem cell
"Alleged 'stem cells' can fail to meet the definition on many counts. Stem cells should persist long term, yet many 'stem cells' exist only in the fetus. Multipotency — the ability to generate multiple cell types — is a criterion for a haematopoietic, or blood-forming, stem cell, but spermatagonial stem cells only produce sperm. Stem cells specific to tissue such as cartilage, the kidney and the cornea have been reported, with varying degrees of acceptance. The quest for a 'stemness signature', a collection of markers common to all stem cells, has been met with frustration."

-significant
"Most statisticians resign themselves to abuse of the term's strict definition. But more grievous trespasses abound. "Statistical significance is neither a necessary nor a sufficient condition for proving a scientific result," says Stephen Ziliak, an economist at Roosevelt University in Chicago, Illinois, and co-author of The Cult of Statistical Significance. P-values are often used to emphasize the certainty of data, but they are only a passive read-out of a statistical test and do not take into account how well an experiment was designed."

-consciousness
"Many definitions of consciousness include the ability to sort through the relentless onslaught of incoming data to create and respond to an internal model of the external world. And some believe that simply gathering data about neurons and behaviours will not be enough."

Histone Code Cracked?

This report in Nature presents genome-wide CHIP maps of a variety of histone modifications in a few types of embryonic and stem cell lineages. Seems like they found some very interesting signatures that correlated well with gene expression status. For example, trimethylation at lysines 4 and 27 could discriminate expressed versus inducible versus repressed genes, whereas the same modification at lysines 4 and 9 marks imprinted regions. Very cool. Of course we'll have to see what the AC has to say for the expert opinion.

I once proposed a similar project in a mock post-doc grant proposal for a systems biology grad class I took (except with the added minor step of cloning mice by somatic cell nuclear transfer). It got pretty bad reviews. Apparently some people thought it was too ambitious. Go figure. This one only took 15 authors...