Latent memory of cells comes to life

New Danish research has examined the mechanisms behind latent cell memory, which can come to life and cause previously non-existent capacities suddenly to appear. Special yeast cells for example, can abruptly change from being of a single sex to hermaphrodite.

Researchers from the Niels Bohr Institute at the University of Copenhagen have used mathematical models and computer simulations to examine fundamental mechanisms of cell memory. The research is an interdisciplinary cooperation between molecular biologists and physicists and has just been published in the prestigious scientific journal CELL where it is featured on the cover page (article by Dodd et al., 18 May issue).

Dormant capacities

Our genetic material - DNA – is a blueprint for how we look and are. This genetic material is very stable and it is faithfully transmitted to our descendants. Once in a while though, a change occurs to the DNA, either large or small. Such changes are at the origin of the immense and varied animal and plant life on earth. Constructive changes in the DNA, that is, changes creating new functions, normally arise by a slow and gradual process that involves natural selection operating over many generations.

Sometimes however, dramatic and very sudden changes are observed in one individual in the absence of any kind of change to the DNA. This happens in fact in all of us as our body develops: cells with identical genetic information adopt very different fates, forming tissues that have apparently very little in common with each other, such as skin, brain, or bones. Mechanisms at the origin of this so-called cellular differentiation are those for which researchers at the University of Copenhagen have a possible clarification.

”The explanation for the sudden changes is that it is not the DNA itself that is altered - it is its immediate surroundings that change and thereby cause a cell to activate some of its dormant capacities” says Kim Sneppen, professor in Biophysics at the Niels Bohr Institute, University of Copenhagen.

The environment controls the DNA

The DNA coils itself around protein complexes called nucleosomes. Importantly, nucleosomes can carry various chemical modifications that either allow, or prevent, the expression of the DNA wrapped around them. Every time a cell divides into new cells, its double-stranded DNA splits into two single strands, which then each produce a new double-strand.

Nucleosomes though are not duplicated like the DNA-strands. Rather, they are distributed between the two new DNA double strands and the empty spaces are filled by new nucleosomes. Cell division is therefore an opportunity for changes in the nucleosomal composition of a specific DNA region. Changes can also happen during the lifetime of a cell due to chemical reactions allowing interconversions between the different nucleosome types. The effect of these changes can be that a latent capacity that was dormant comes to life, or, conversely, that a previously active capacity shuts down.

Same inheritance – different traits

In the practical experiment molecular biologists used a mutant of a yeast cell which was bi-stable, in that it could become either of a single sex or hermaphrodite. The experiment showed that a spontaneous change occurred in the yeast cells about every 2000 cell-generations. By building a mathematical model based on positive feedback from the microscopic state of the nucleosomes, the research group could simulate the experimental results and in this way gained insight into the mechanisms by which living cells with identical DNA can achieve extreme differentiation.

The research at the ‘Models of Life’ Basic Research Center at the Niels Bohr Institute has shown that communication between nucleosomes and positive feedback are likely to constitute fundamental memory mechanisms in individual cells. The mechanism gives both stability and openness to new influences which the cell could need to change state. Nature has a partner which controls the cells latent memory.

Source: University of Copenhagen

Related stories:

A breakthrough, then a surge, in stem cell research
Less than a year after a Wisconsin team helped discover a major alternative to human embryonic stem cells, the Madison scientists say more than 800 labs have begun using the approach, suggesting that many stem-cell researchers are starting to move beyond controversial embryonic sources for their work.
Landmark study unlocks stem cell, DNA secrets to speed therapies
In a groundbreaking study led by an eminent molecular biologist at Florida State University, researchers have discovered that as embryonic stem cells turn into different cell types, there are dramatic corresponding changes to the order in which DNA is replicated and reorganized.
Nobel prizewinner describes his chemistry research as ‘a 1970s disco light'
Columbia University professor Martin Chalfie called the subject of his Nobel Prize-winning research "a 1970s disco light" that traces the growth of diseases such as cancer and Alzheimer's.
New findings may improve treatment of inherited breast cancer
Scientists have identified some of the elusive downstream molecules that play a critical role in the development and progression of familial breast cancer. The research, published by Cell Press in the October 10th issue of the journal Molecular Cell, also identifies a compound found in grapes and red wine as an excellent candidate for treatment of some forms of breast cancer.
Scientists pinpoint key proteins in blood stem cell replication
A family of cancer-fighting molecules helps blood stem cells in mice decide when and how to divide, say researchers at the Stanford University School of Medicine. Blocking the molecules' function spurs the normally resting cells to begin proliferating strangely - making too much of one kind of cell and not enough of another. Many types of human blood cancers involve a similar disruption in the expression of that same family of molecules.
Using living cells as nanotechnology factories
In the tiny realm of nanotechnology, scientists have used a wide variety of materials to build atomic scale structures. But just as in the construction business, nanotechnology researchers can often be limited by the amount of raw materials. Now, Biodesign Institute at Arizona State University researcher Hao Yan has avoided these pitfalls by using cells as factories to make DNA based nanostructures inside a living cell.
New research may help to design better gene therapy vectors
(PhysOrg.com) -- Research published by scientists from the University of Reading may offer an insight into ways of making safer and more specific gene therapy vectors. The research, published in the journal Nature Structural and Molecular Biology, describes the structure of the viral fusion protein gp64, which is involved in the mechanism which viruses use to invade host cells. In the past, Bacloviruses have been suggested as possible gene therapy vectors due to the way in which they enter host cells, but there has been little evidence which explain these properties up to now.
New blood test for Down syndrome
Howard Hughes Medical Institute researchers have developed a new prenatal blood test that accurately detected Down syndrome and two other serious chromosomal defects in a small study of 18 pregnant women. If confirmed in larger trials, they say, the test would offer a safer and faster alternative to invasive prenatal tests such as amniocentesis that pose a small risk of miscarriage.

News discussion:

General Science news