Off Tangent Comix

DSM-V Update
 
Leave a comment.
 
See continuing updates on the APA, DSM, and the upcoming DSM Fifth Edition (DSM-V).
 
See our Annotated List of DSM-related news, research reports, analyses, and opinion pieces.
 
Visit the TS-Si Article Archive for reports on science, medicine, government, society, and other topics.
Chad A. Mirkin, Northwestern University, George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences. Photo by Bill Arsenault. 

DNA Blueprints Guide The Construction Of Specific Human Structures

Chad Mirkin discusses using DNA to build a three-dimensional structure out of gold, likening the process to building a house. Starting with basic materials such as bricks, wood, siding, stone and shingles, a construction team can build many different types of houses out of the same building blocks.
 
The article includes an audio recording of the full interview. Photo courtesy of the UCSD School of Medicine.
Same Nucleotide Sequence In Two People, Different Results Print E-mail
Science - Genetics & Genome
TS-Si News Service   
Thursday, 24 April 2008 17:00
Together, DNA and histone proteins form nucleosomes, and nucleosome fibers fold into loops of chromatin.Cold Spring Harbor, NY, USA. Sometimes there are changes in gene expression that remain stable through continuing rounds of cell division (sometimes between generations), but do not involve any changes in the organism's underlying DNA sequence of the organism. A team of scientists at Cold Spring Harbor Laboratory (CSHL) has solved another in a series of mysteries about this critical mechanism of gene expression. Their findings appear in Current Biology.
 
Letters representing the three billion pairs of molecules that form the “rungs” of the helical DNA “ladder” are routinely called the human “genetic code.” The human code is comprised of DNA that transmits traits across generations in a variety of ways, not all of which depend on the sequence of letters in the code. 
 
RNA Interference Guides Histone Modification during the S Phase of Chromosomal Replication. Anna Kloc, Mikel Zaratiegui, Elphege Nora, and Rob Martienssen. Current Biology 18(7): 490-495, 08 April 2008.
In some cases, rather than the sequence of “letters,” it is the physical manner in which DNA is spun around protein spools called histones and tightly packed into chromosomes that determines whether or with what intensity specific genes are expressed.

Inherited Clumping

The same sequence of nucleotides in two people can produce different patterns of gene expression if the way the DNA is clumped happens to be different.Rob Martienssen of CSHL, who led the research team, says about a tenth of our DNA stands aloof.
 

 
Visualizing DNA. The findings of molecular research enable modeling and animation of DNA as it is copied in living cells. An assembly line of biochemical machines pull apart the DNA double helix and produce a copy of each strand.
 
Every cell has 6 feet of the long DNA molecule that has been densely packed, or wrapped, into the tiny nucleus. The process starts when DNA is wrapped around special protein molecules called histones. The combined loop of DNA and protein is called a nuclei zone which is then packed into a thread.
 
The end result is a fiber known as chromatin, which is looped and coiled again, leading to the familiar shapes known as chromosomes. They can be seen in the nucleus of dividing cells. Chromosomes are not always present — they form around the time cells divide when the two copies of the cell's DNA need to be separated.
 
Video: Adapted from a presentation by Drew Barry at The Walter and Eliza Hall Institute of Medical Research.
Time 03:16
 
For more, see these
The idle DNA spends its time in tightly packed clumps called heterochromatin, and unwinding only to replicate when a cell divides.
 
After copying, both of the resulting DNA molecules — to the surprise of many — have been observed to form reclusive clumps in the same places as the original one did. 
 
This inherited clumping of DNA, which causes genes to be expressed in distinctive ways, is one of a series of phenomena that scientists call epigenetic. The same sequence of nucleotides in two people can produce different patterns of gene expression if the way the DNA is clumped happens to be different.
 
Probing Epigenetics in Yeast
 
CSHL professor Rob Martienssen, Ph.D., who led the research team.“We have not understood epigenetic inheritance very well,” says CSHL professor Rob Martienssen, Ph.D., a plant geneticist and one of the pioneers in the study of epigenetics.
 
To explore this process, Martienssen and his team are studying the way DNA is packed in yeast, and how this packing can be transmitted across generations. The single-cell yeast organism is easy to study, in part because it lacks other epigenetic inheritance mechanisms, such as chemical modifications of DNA, that complicate the study of more complex animals and plants.
 
Long DNA molecules cram into cell nuclei that are almost a million times smaller than they are. They do so by wrapping around proteins called histones, which array themselves along the length of the DNA molecule like beads on a string. These DNA-wrapped histones then form larger arrays. The densely packed mass is then modified chemically by other proteins to form heterochromatin. 
 
The dense packing of heterochromatin hides the DNA sequence from the cellular machinery that reads its genetic information, so the DNA in heterochromatin is “silenced.” The genes it contains are effectively turned off.
 
Surprisingly, the clumping persists even after cells divide, although, says Dr. Martienssen, “it’s always been a mystery how modifications of histones could be inherited.” A few years ago, however, his group and others solved this mystery. They found that histone modification is controlled by complicated cellular mechanisms broadly known as RNA interference, or RNAi.
 
In RNAi, RNA that is copied from particular regions of DNA interacts with various proteins to modify histones in the same regions. Because the RNA matches only the section of DNA that produced it, it “provides the specificity that you need to make sure that only that part of the chromosome gets these histone modifications,” Dr. Martienssen says. “If the whole chromosome were to get those histone modifications, you’d be dead.”
 
All in the Timing
 
These results raised a new puzzle, though: Since genes contained within heterochromatin are silenced, how can they give rise to the RNA molecules that help to modify histones? In new research, Martienssen’s team has now solved this puzzle by tracking the cells through their cycle of growth and division.
 
They found that the interfering RNA molecules appear only during the brief part of the cell cycle when DNA is replicating. This result, Martienssen says, “neatly accounts for the paradox about how ‘silent’ heterochromatin can be transcribed [into interfering RNA], because it’s transcribed only in a narrow window of the cell cycle.”
 
The researchers also found that RNAi varies strongly with temperature. They speculate that this variation is responsible for inherited traits such as vernalization, the well-known process by which certain plants must be exposed to low temperatures before they will flower.
 
Indeed, Martienssen says, there is “a whole slew of epigenetic phenomena that are sensitive to temperature.”
CitationRNA Interference Guides Histone Modification during the S Phase of Chromosomal Replication. Anna Kloc, Mikel Zaratiegui, Elphege Nora, and Rob Martienssen. Current Biology 18(7): 490-495, 08 April 2008.
Download PDF
Supp Data
Summary

Background. Heterochromatin is chromosomal material that remains condensed throughout the cell division cycle and silences genes nearby. It is found in almost all eukaryotes, and although discovered (in plants) almost 100 years ago, the mechanism by which heterochromatin is inherited has remained obscure. Heterochromatic silencing and histone H3 lysine-9 methylation (H3K9me2) depend, paradoxically, on heterochromatic transcription and RNA interference (RNAi).

Results. Here, we show that heterochromatin protein 1 in fission yeast (Swi6) is lost via phosphorylation of H3 serine 10 (H3S10) during mitosis, allowing heterochromatic transcripts to transiently accumulate in S phase. Rapid processing of these transcripts into small interfering RNA (siRNA) promotes restoration of H3K9me2 and Swi6 after replication when cohesin is recruited. We also show that RNAi in fission yeast is inhibited at high temperatures, providing a plausible mechanism for epigenetic phenomena that depend on replication and temperature, such as vernalization in plants and position effect variegation in animals.

Conclusions. These results explain how “silent” heterochromatin can be transcribed and lead to a model for epigenetic inheritance during replication.
TS-Si News ServiceThe TS-Si News Service is a collaborative effort by TS-Si.org editors, contributors, and corresponding institutions. The sources can include the cited individuals and organizations, as well as TS-Si.org staff contributions. Articles and news reports do not necessarily convey official positions of TS-Si, its partners, or affiliates. We welcome your comments. Use the form below to leave a public comment or send private correspondence via the TS-Si Contact Page. We will not divulge any personal details or place you on a mailing list without your permission.
Comments (0)Add Comment
feedSubscribe to this comment's feed
min/maxShow/Hide comments

Write comment
feedShow/Hide comment form

security code
Write the displayed characters


busy
< Prev   Next >
Last Updated on Saturday, 13 December 2008 22:47