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How are epigenetic marks transmitted during cell division?

How are epigenetic marks transmitted during cell division?



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As far as I know, this is one of the biggest questions in the epigenetic field: how are the epigenetic marks like histone modifications propagated through cell division? A lot is already known about DNA methylation (e.g. as in How does “inheritance of methylation” of DNA and/or histones work?), but very little about histone modifications. What is the current state of knowledge?


I can get the ball rolling…

Found a nice paper which looks at this phenomenon in yeast.

So as a primer, 8 histone proteins come together to make a spool of sorts which DNA wraps around:

Histone proteins have many sequence variants, and each one of them can be covalently modified with methyl, acyl, phospho, SUMO, adp and many other sorts of chemical groups via a chemical bond. Although its not yet clear exactly how it works its clear that these modifications can change the behavior of the histones which prevent transcription of the gene when they have the chromosomal DNA all wrapped up.

So as to the question a pattern of inheritance of modified histone patterns is indeed seen and has epigenetic effects. (that is, it modifies the genetic phenotype of daughter cells which retain the histone modifications of the parent cells). In this paper, newly synthesized (and labelled) yeast histone can be found incorporated into certain segments of the genome, which demonstrates that large segments of the histones are carried forward from the parent cell.

They also found a particular case of histone epigenetic labeling carried forward through division:

Furthermore, if the heterochromatin-binding protein Sir3 is unavailable during DNA replication, histone H3-K4

So there's evidence that histone configurations are transmitted epigenetically, In this 2011 paper, the author support a 'conservative distribution model' and compare it to a 'semi-conservative' model:

The conservative distribution model proposes that newly synthesized histone molecules form nucleosomes that are randomly inserted among preexisting parental nucleosomes.

The semi-conservative distribution model proposes that a hybrid nucleosome that contains both newly synthesized and parental histone H3-H4 dimers is formed, which facilitates the transmission of epigenetic information within the basic nucleosome unit.

They go on to say that a conservative model of histone inheritance allows for strong epigenetic inheritance as the remaining parent histones will tend to attract similarly labelled histones as the new histones incorporate themselves among the parental histones on the daughter chromosome.

Its still being worked out though…


Epigenetics and Behavior by Eva Jablonka, Zohar Bronfman

Behavioral epigenetics is part of the thriving field of epigenetics, which describes the study of developmental processes that lead to persistent changes in the states of organisms, their components, and their lineages. Such developmental, context-sensitive changes are mediated by epigenetic mechanisms that establish and maintain the changes in patterns of gene expression and cellular structures that occur during ontogeny in both nondividing cells, such as most mature neurons, and dividing cells such as stem cells. When information is vertically transmitted to cells during cell division, or horizontally between cells through migrating reproducing molecules (like small RNAs), and when variations in the transmitted information are not determined by variations in DNA sequence (i.e., the same DNA sequence has more than one cell-heritable epigenetic state), epigenetic inheritance is said to occur. Behavioral epigenetics investigates the role of behavior in the shaping of developmental epigenetic states and the reciprocal role of epigenetic factors and mechanisms in the shaping of the behavior of human and nonhuman animals, at the short-, middle-, and long-term (ontogenetic, ecological, and evolutionary) time scales. The focus is on the molecular-epigenetic study of the interactions between environmental factors, such as ecological factors and habitual activities such as lifestyles and learning, with genetic variation and the neurobiological and physiological mechanisms that mediate between the regulation of gene expression and behavior. This range of epigenetic processes therefore includes, but is not limited to, studies involving epigenetic inheritance and the direct and indirect evolutionary effects of epigenetic developmental mechanisms. The neural-behavioral aspects that occur during ontogeny through the mediation of epigenetic mechanisms are central to behavioral epigenetics and are the main focus of neural epigenetics.


Epigenetics basics

After fertilization, the egg cell divides. Up to the 8-cell stage, all daughter cells are equal. They are called totipotent because each of them is still capable of producing a complete organism on its own.

After this stage, there are cells with a different internal program. These cells have limited development potential as it becomes more and more specialized.

When the body is fully formed, most body cells are firmly programmed for their function based on epigenetic mechanisms. The function was fixed due to biochemical modifications of the bases in DNA or the histones packaging the DNA, or both. The sequence of the genetic material remains unchanged apart from a few random mutations.

Such epigenetic modifications result in certain regions of the genome being “silenced”, i.e. cannot be easily transcribed into RNA for protein synthesis. These modifications look quite different in somatic cells than in stem cells or in germ cells. The most important modifications are the methylation of cytosine bases and the side-chain methylation and acetylation of histones.

Besides methylation, telomeres have an important epigenetic influence. Telomeres protect the ends of chromosomes from degradation during cell division. The enzyme telomerase ensures that the chromosomes remain intact. Mental stress can reduce the activity of this enzyme, ultimately led to an accelerated shortening of telomeres in the aging process.


Question: How Are The Epigenetic Marks Of A Particular Chromatin State Preserved During Cell Division? A. Parental, Marked H2A-H2B Dimers Stay Associated With Strands After Replication And Recruit New H3-H4 Tetramers. B. H2A-H2B Dimers And H3-H4 Tetramers Come Off During Replication And Assemble With Unmarked Histones. These New Octamers Then Rebind To The Newly .

How are the epigenetic marks of a particular chromatin state preserved during cell division?

a. Parental, marked H2A-H2B dimers stay associated with strands after replication and recruit new H3-H4 tetramers.

b. H2A-H2B dimers and H3-H4 tetramers come off during replication and assemble with unmarked histones. These new octamers then rebind to the newly replicated DNA to form nucleosomes

c. Parental, marked H3-H4 tetramers stay associated with strands after replication and recruit new H2A-H2B dimers.

d. Histone chaperones make sure that at least one component of each new nucleosome is marked


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A model for transmission of the H3K27me3 epigenetic mark. / Hansen, Klaus H. Bracken, Adrian P. Pasini, Diego Dietrich, Nikolaj Gehani, Simmi S. Monrad, Astrid Rappsilber, Juri Lerdrup, Mads Helin, Kristian.

In: Nature Cell Biology , Vol. 10, No. 11, 2008, p. 1291-1300.

Research output : Contribution to journal › Article › peer-review

T1 - A model for transmission of the H3K27me3 epigenetic mark

N2 - Organization of chromatin by epigenetic mechanisms is essential for establishing and maintaining cellular identity in developing and adult organisms. A key question that remains unresolved about this process is how epigenetic marks are transmitted to the next cell generation during cell division. Here we provide a model to explain how trimethylated Lys 27 of histone 3 (H3K27me3), which is catalysed by the EZH2-containing Polycomb Repressive Complex 2 (PRC2), is maintained in proliferating cells. We show that the PRC2 complex binds to the H3K27me3 mark and colocalizes with this mark in G1 phase and with sites of ongoing DNA replication. Efficient binding requires an intact trimeric PRC2 complex containing EZH2, EED and SUZ12, but is independent of the catalytic SET domain of EZH2. Using a heterologous reporter system, we show that transient recruitment of the PRC2 complex to chromatin, upstream of the transcriptional start site, is sufficient to maintain repression through endogenous PRC2 during subsequent cell divisions. Thus, we suggest that once the H3K27me3 is established, it recruits the PRC2 complex to maintain the mark at sites of DNA replication, leading to methylation of H3K27 on the daughter strands during incorporation of newly synthesized histones. This mechanism ensures maintenance of the H3K27me3 epigenetic mark in proliferating cells, not only during DNA replication when histones synthesized de novo are incorporated, but also outside S phase, thereby preserving chromatin structure and transcriptional programs.

AB - Organization of chromatin by epigenetic mechanisms is essential for establishing and maintaining cellular identity in developing and adult organisms. A key question that remains unresolved about this process is how epigenetic marks are transmitted to the next cell generation during cell division. Here we provide a model to explain how trimethylated Lys 27 of histone 3 (H3K27me3), which is catalysed by the EZH2-containing Polycomb Repressive Complex 2 (PRC2), is maintained in proliferating cells. We show that the PRC2 complex binds to the H3K27me3 mark and colocalizes with this mark in G1 phase and with sites of ongoing DNA replication. Efficient binding requires an intact trimeric PRC2 complex containing EZH2, EED and SUZ12, but is independent of the catalytic SET domain of EZH2. Using a heterologous reporter system, we show that transient recruitment of the PRC2 complex to chromatin, upstream of the transcriptional start site, is sufficient to maintain repression through endogenous PRC2 during subsequent cell divisions. Thus, we suggest that once the H3K27me3 is established, it recruits the PRC2 complex to maintain the mark at sites of DNA replication, leading to methylation of H3K27 on the daughter strands during incorporation of newly synthesized histones. This mechanism ensures maintenance of the H3K27me3 epigenetic mark in proliferating cells, not only during DNA replication when histones synthesized de novo are incorporated, but also outside S phase, thereby preserving chromatin structure and transcriptional programs.


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Dosage Compensation in Mammals

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Chromosome Folding: Driver or Passenger of Epigenetic State?

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Enhancer RNAs: A Class of Long Noncoding RNAs Synthesized at Enhancers

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Transcriptional Silencing by Polycomb-Group Proteins

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Transcriptional Regulation by Trithorax-Group Proteins

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Structural and Functional Coordination of DNA and Histone Methylation

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DNA Methylation in Mammals

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Histone H3 Mutations in Pediatric Brain Tumors

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Cellular Reprogramming

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A Brief History of Epigenetics

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Edith Heard, the Epigenetics Revolution

This is a discipline that has been booming since the early 2000s and the hopes, or even fantasies, it arouses have been the subject of extensive coverage. Epigenetics participates in regulating the expression of our genes through epigenetic marks. These chemical modifications to DNA help the cells in our body to acquire, and above all maintain, their identity during development. But they are also reversible, which opens perspectives for curing certain diseases that involve the epigenome. This January, a renowned global specialist in epigenetics, the biologist Edith Heard became director general of the prestigious European Molecular Biology Laboratory (EMBL), an intergovernmental research organisation that includes 29 countries. She told us more about her work and her new missions.

What is the origin of the term epigenetics?
Edith Heard: It was invented in 1942 by the British biologist Conrad Waddington in order to reconcile the worlds of genetics (genes were discovered at the turn of the 20th century) and embryology. Geneticists were focusing on heredity and the traits transmitted to subsequent generations, while embryologists were asking how they were put in place during development. Waddington wanted to create a new discipline that would cover embryogenesis (also called epigenesis since the 17th century) and genetics, so "epigenetics" combined these two words. This notion has evolved since then we have discovered DNA and, with some initial disbelief, observed that all the cells in our body have the same DNA as the fertilised egg, although there are still differences between a liver cell, muscle cell or neuron, for example. Because the entire DNA code is conserved in the cells, the question posed by scientists was therefore how cells acquire their own identity, and how this is maintained during cell division. That’s how we arrived at our modern definition of epigenetics.

And what is that definition?
E. H.: Epigenetics refers to any change to gene expression that does not involve a modification of the DNA sequence, which is stable but remains reversible. We now know that cells acquire and keep their identity thanks to epigenetic marks: chemical differences in the DNA that never alter its sequence but make it possible to read certain genes and not others. So epigenetics is a sort of cell memory that is transmissible to future generations of cells. However, it is one that can be deleted, hence the term reversibility.

In the early 1980s, a scientist called Peter Jones experienced this phenomenon by chance. He was culturing mouse skin cells (fibroblasts) in a Petri dish, to which he had added a molecule, 5-azacytidine. A few days later, to his surprise, cells had appeared in the culture and looked completely different. He initially thought his sample had been contaminated by fungi, but it actually turned out that these cells were myotubes, or muscle cells. The 5-azacytidine had deleted the epigenetic marks of the embryonic cells and reprogrammed them as muscle cells!

Hence the idea sometimes put forward that epigenetics has put an end to the reign of the “all-genome”, this tenacious determinism imposed by our genetic code.
E. H.: It is an attractive theory, but partially false, because it is indeed the genetic code that decides to read certain genes (or not), thanks to proteins called transcription factors! The epigenetic machinery comes just after that: the purpose of the epigenetic marks that bind to the genes is to maintain this choice throughout cell divisions.

How did you become interested in epigenetics? You had initially trained in pure genetics.
E. H.:
After my studies at Cambridge, I completed my PhD in cancer research at the Imperial Cancer Research Fund in London. I wanted to know why some parts of the genome are amplified in certain cancer cells, or in other words why there are several copies of the same genes. To look at the genome, we cut it with restriction enzymes obtained from bacteria, but this did not work when epigenetic marks were present. That’s how I became interested in epigenetics—it was for purely technical reasons! I found the article by Peter Jones and ordered the same molecule, 5-azacytidine, so as to be able to remove the epigenetic marks and cut the genome as I wished. I entered the world of chemical modifications through these manipulations.

You mentioned the specialisation of cells into skin or muscle cells, etc. Inversely, body cells can become stem cells again after the epigenetic marks have been removed, as demonstrated by Shinya Yamanaka, laureate of the Nobel Prize in Physiology or Medicine in 2012.
E. H.:
That’s absolute proof that the genetic code is wholly conserved in somatic cells (editor’s note: the cells in our body). Nevertheless, this change does not occur at the click of a finger. Even using the right products, it takes three weeks to delete the epigenetic marks carried by the DNA in skin cells, and obtain induced pluripotent stem cells (iPSC) that are similar to embryonic stem cells. Indeed, the epigenetic marks tend to resist. That’s what I call the "epigenetic barrier", which prevents a change in the identity of our cells and protects the phenotype (appearance) of the multicellular beings that we are.

Epigenetics has also aroused many fantasies. The notions of reversibility and heritability, in particular, have given rise to a variety of interpretations. Epigenetic marks may be influenced by our environment, the air we breathe or the stress we experience—and transmissible to our children and grandchildren, for example. As a scientist, what is your position on this issue?
E. H.:
I imagine you are referring to the epidemiological study on the consequences of the famine that affected the Netherlands during the Second World War. The children, and perhaps the grandchildren, of pregnant women who at that time could not ingest more than a few calories a day for weeks on end, may now be experiencing health problems linked to a dysfunctional metabolism. According to the study, this was due to changes that affected epigenetic modifications as a result of the famine, and these may have been transmitted to the children and then the grandchildren of these malnourished women.

As another example, some even claim that the stress suffered by Holocaust survivors may have been transmitted to subsequent generations via epigenetic marks. At present, there is no solid proof of this at the molecular biology level. And we all know that our behaviour, and the way we bond with our descendants, is a potent vector for transmission. All these fantasies surrounding epigenetics are both an incentive for scientists (because they reflect society’s interest in our work) and a drawback as they induce expectations we cannot always meet, potentially leading to frustration with our discipline. Science is still laying the molecular foundations of epigenetics, and they are 100% fundamental.

Mention is nevertheless often made of "epidrugs" which could help to cure certain cancers. What is the situation here?
E. H.:
In all cancers, the distribution of epigenetic modifications is abnormal. For a long time, it was even postulated that the genes involved in the initiation of a tumour were epigenetically modified. Hence the interest in epidrugs : these molecules, which have been known for several decades (they were used in chemotherapy even before we understood how they functioned) do indeed act on epigenetic modifications, and in particular on the best known of them, DNA methylation. Thanks to the high-throughput sequencing of tumour genomes, we have found out that most tumours are due to mutations that directly affect the DNA sequence of so-called “driver” genes in other words, those that lead to the development of a tumour. What’s surprising is that some of these mutations also affect the genes involved in epigenetic processes. This explains the generalisation of epigenetic modifications in tumours. The problem with cancer is that nothing is simple: genes are mutated, the genome is altered, and so is the epigenome, but we still don’t know whether these changes are related and in which direction they occur. The use of epidrugs also brings up a number of issues, as they do not only target one or two genes but all the epigenetic marks of an individual, with consequences that we cannot fully control at this stage. This is where we stand at present on cancer and epigenetics. It is a research field that raises high hopes but is not progressing very rapidly. Once again, it requires an enormous amount of basic research. Unlike the genome, which has been completely deciphered, we still don’t know everything about the epigenome, particularly as far as cancer is concerned.


Inheritance and Transmission of Epigenetic Memory Across Generations

New research has been suggesting that parents can transmit changes to their gene expression to their children. The heritable changes occur as a result of environmental stresses and are known as epigenetic modifications. A previous article covered the epigenetic transfer of nutrition &ldquomemory&rdquo across several generations. Now, a recent study by researchers from the University of California in Santa Cruz, demonstrates the transferring of epigenetic memory across generations as well as from one cell to another during early development.

The new study, published in Science, looked at a well-studied, common epigenetic modification &ndash histone methylation . They focused on histone H3, a protein involved in DNA packaging. Specifically, the researchers investigated the methylation of histone H3 on Lys27 (H3K27me) by Polycomb repressive complex 2 (PRC2). This has previously been shown to repress or turn off genes. This particular epigenetic mark is widespread and can be found in every multicellular animal &ndash from the small roundworm investigated in the current study, C. elegans, to humans.

This image depicts the inheritance and transmission of the epigenetic mark H3K27me3 in C. elegans. The 1-cell embryo (left) shows the histone methylation mark (green) inherited on sperm chromosomes but not on the oocyte chromosomes (pink) contributed by a C. elegans mother who was mutated, knocking out the methylation enzyme PRC2. The 2-cell embryo (right) shows transmission of the histone methylation mark on the sperm-derived chromosomes in each daughter nucleus.
Credit: Laura J. Gaydos

Susan Strome, the corresponding author and professor of molecular, cell and developmental biology at UC Santa Cruz said, &ldquoThere has been ongoing debate about whether the methylation mark can be passed on through cell divisions and across generations, and we&rsquove now shown that it is.&rdquo

Along with first author Laura Gaydos, who led the study for her Ph.D. thesis, and co-author Wenchao Wang, the team created worms in the lab with a mutation that knocks out the enzyme that makes the methylation mark. They then bred the mutated C. elegans with normal C. elegans. The researchers used fluorescent labeling to keep track of the marked and unmarked chromosomes from sperm and egg cells to the embryo cells that undergo division after fertilization.

When the mutant egg cells were fertilized by normal C. elegans sperm, the embryos had six chromosomes that were methylated (from the sperm) and six &ldquonaked&rdquo chromosomes that were unmarked (from the egg).

During embryo development, the chromosomes are replicated and the cells divide. The scientists discovered when a chromosome with a methylation mark replicates, the mark is also found on the two daughter chromosomes. Without the enzyme (PRC2) necessary for histone methylation, however, the methylation marks are diluted over time after each cell division.

&ldquoThe mark stays on the chromosomes derived from the initial chromosome that had the mark, but there&rsquos not enough mark for both daughter chromosomes to be fully loaded,&rdquo Strome said. &ldquoSo the mark is bright in a one-cell embryo, less bright after the cell divides, dimmer still in a four-cell embryo, and by about 24 to 48 cells we can&rsquot see it anymore.&rdquo

They then repeated the same experiment, this time using mutant C. elegans sperm to fertilize normal C. elegans eggs. PRC2 is not typically present in sperm cells, which don&rsquot contribute much more to the embryo than their chromosomes. However, PRC2 is present in egg cells. They found the same results as before, with six chromosomes that were methylated (this time from the egg) and six &ldquonaked&rdquo chromosomes that were unmarked (this time from the sperm). But now, the embryos also had the enzyme.

&ldquoRemarkably, when we watch the chromosomes through cell divisions, the marked chromosomes remain marked and stay bright, because the enzyme keeps restoring the mark, but the naked chromosomes stay naked, division after division,&rdquo Strome said. &ldquoThat shows that the pattern of marks that was inherited is being transmitted through multiple cell divisions.&rdquo

Strome indicated that the investigators&rsquo findings about the inheritance of histone methylation marks in C. elegans also applies to other organisms, although various organisms utilize the repressive marker to regulate different genes at different times of development. The same enzyme is used by all animals to make the same methylation mark as an indicator for gene repression. Strome shared that her colleagues studying epigenetics related to mice and humans are excited about the study&rsquos results.

&ldquoTransgenerational epigenetic inheritance is not a solved field&ndashit&rsquos very much in flux,&rdquo she said. &ldquoThere are dozens of potential epigenetic markers. In studies that document parent-to-child epigenetic inheritance, it&rsquos not clear what&rsquos being passed on, and understanding it molecularly is very complicated. We have a specific example of epigenetic memory that is passed on, and we can see it in the microscope. It&rsquos one piece of the puzzle.&rdquo

Source: Learn all about it and read more about their findings here: L. J. Gaydos, W. Wang, S. Strome. H3K27me and PRC2 transmit a memory of repression across generations and during development. Science. 2014.


Study shows how epigenetic memory is passed across generations

A growing body of evidence suggests that environmental stresses can cause changes in gene expression that are transmitted from parents to their offspring, making "epigenetics" a hot topic. Epigenetic modifications do not affect the DNA sequence of genes, but change how the DNA is packaged and how genes are expressed. Now, a study by scientists at the University of California, Santa Cruz, shows how epigenetic memory can be passed across generations and from cell to cell during development.

The study, published September 19 in Science, focused on one well studied epigenetic modification--the methylation of a DNA packaging protein called histone H3. Methylation of a particular amino acid (lysine 27) in histone H3 is known to turn off or "repress" genes, and this epigenetic mark is found in all multicellular animals, from humans to the tiny roundworm C. elegans that was used in this study.

"There has been ongoing debate about whether the methylation mark can be passed on through cell divisions and across generations, and we've now shown that it is," said corresponding author Susan Strome, a professor of molecular, cell and developmental biology at UC Santa Cruz.

Strome's lab created worms with a mutation that knocks out the enzyme responsible for making the methylation mark, then bred them with normal worms. Using fluorescent labels, they were able to track the fates of marked and unmarked chromosomes under the microscope, from egg cells and sperm to the dividing cells of embryos after fertilization. Embryos from mutant egg cells fertilized by normal sperm had six methylated chromosomes (from the sperm) and six unmarked or "naked" chromosomes (from the egg).

As embryos develop, the cells replicate their chromosomes and divide. The researchers found that when a marked chromosome replicates, the two daughter chromosomes are both marked. But without the enzyme needed for histone methylation, the marks become progressively diluted with each cell division.

"The mark stays on the chromosomes derived from the initial chromosome that had the mark, but there's not enough mark for both daughter chromosomes to be fully loaded," Strome said. "So the mark is bright in a one-cell embryo, less bright after the cell divides, dimmer still in a four-cell embryo, and by about 24 to 48 cells we can't see it anymore."

The researchers then did the converse experiment, fertilizing normal egg cells with mutant sperm. The methylation enzyme (called PRC2) is normally present in egg cells but not in sperm, which don't contribute much more than their chromosomes to the embryo. So the embryos in the new experiment still had six naked chromosomes (this time from the sperm) and six marked chromosomes, but now they also had the enzyme.

"Remarkably, when we watch the chromosomes through cell divisions, the marked chromosomes remain marked and stay bright, because the enzyme keeps restoring the mark, but the naked chromosomes stay naked, division after division," Strome said. "That shows that the pattern of marks that was inherited is being transmitted through multiple cell divisions."

Strome noted that the findings in this study of transmission of histone methylation in C. elegans have important implications in other organisms, even though different organisms use the repressive marker that was studied to regulate different genes during different aspects of development. All animals use the same enzyme to create the same methylation mark as a signal for gene repression, and her colleagues who study epigenetics in mice and humans are excited about the new findings, Strome said.

"Transgenerational epigenetic inheritance is not a solved field--it's very much in flux," she said. "There are dozens of potential epigenetic markers. In studies that document parent-to-child epigenetic inheritance, it's not clear what's being passed on, and understanding it molecularly is very complicated. We have a specific example of epigenetic memory that is passed on, and we can see it in the microscope. It's one piece of the puzzle."


Workshops

Epigenetics refers to information transmitted during cell division other than the DNA sequence per se, and it is the language that distinguishes stem cells from somatic cells, one organ from another, and even identical twins from each other. In contrast to the DNA sequence, the epigenome is relatively susceptible to modification by the environment as well as stochastic perturbations over time, adding to phenotypic diversity in the population. Despite its strong ties to the environment, epigenetics has never been well reconciled to evolutionary thinking, and in fact there is now strong evidence against the transmission of so-called “epi-alleles,” i.e. epigenetic modifications that pass through the germline.

However, genetic variants that regulate stochastic fluctuation of gene expression and phenotypes in the offspring appear to be transmitted as an epigenetic or even Lamarckian trait. Furthermore, even the normal process of cellular differentiation from a single cell to a complex organism is not understood well from a mathematical point of view. There is increasingly strong evidence that stem cells are highly heterogeneous and in fact stochasticity is necessary for pluripotency. This process appears to be tightly regulated through the epigenome in development. Moreover, in these biological contexts, “stochasticity” is hardly synonymous with “noise”, which often refers to variation which obscures a “true signal” (e.g., measurement error) or which is structural, as in physics (e.g., quantum noise). In contrast, “stochastic regulation” refers to purposeful, programmed variation the fluctuations are random but there is no true signal to mask.

This workshop will serve as a forum for scientists and engineers with an interest in computational biology to explore the role of stochasticity in regulation, development and evolution, and its epigenetic basis. Just as thinking about stochasticity was transformative in physics and in some areas of biology, it promises to fundamentally transform modern genetics and help to explain phase transitions such as differentiation and cancer.

This workshop will include a poster session a request for poster titles will be sent to registered participants in advance of the workshop.

Organizing Committee

Adam Arkin (University of California, Berkeley (UC Berkeley))
Andrew Feinberg (Johns Hopkins University)
Don Geman (Johns Hopkins University, Applied Mathematics and Statistics)


Watch the video: Was ist eine Funktion? - Einfach erklärt (August 2022).