 |
|
Scientists Clarify a Mechanism of Epigenetic Inheritance
April 23, 2008Although 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 DNA they comprise transmits traits across generations in a variety of ways, not all of which depend on the sequence of letters in the code.
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. 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, described in a paper in the April 8 issue of Current Biology.
Inherited Clumping
According to CSHL professor Rob Martienssen, Ph.D., who led the research team, about a tenth of our DNA stands aloof, spending 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
"We have not understood epigenetic inheritance very well," says Dr. Martienssen, a plant geneticist and one of the pioneers in the study of epigenetics. To explore this process, he 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 almost miraculously 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."
"RNA Interference Guides Histone Modification during the S Phase of Chromosomal Replication" appears in the April 8, 2008, edition of Current Biology. The complete citation is as follows: Anna Kloc, Mikel Zaratiegui, Elphege Nora and Rob Martienssen. The paper is available online at:
http://www.current-biology.com/content/article/abstract?uid=PIIS0960982208003163.
Cold Spring Harbor Laboratory is a private, nonprofit research and education institution dedicated to exploring molecular biology and genetics in order to advance the understanding and ability to diagnose and treat cancers, neurological diseases and other causes of human suffering.
Cold Spring Harbor Laboratory
According to CSHL professor Rob Martienssen, Ph.D., who led the research team, about a tenth of our DNA stands aloof, spending 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
"We have not understood epigenetic inheritance very well," says Dr. Martienssen, a plant geneticist and one of the pioneers in the study of epigenetics. To explore this process, he 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 almost miraculously 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."
"RNA Interference Guides Histone Modification during the S Phase of Chromosomal Replication" appears in the April 8, 2008, edition of Current Biology. The complete citation is as follows: Anna Kloc, Mikel Zaratiegui, Elphege Nora and Rob Martienssen. The paper is available online at:
http://www.current-biology.com/content/article/abstract?uid=PIIS0960982208003163.
Cold Spring Harbor Laboratory is a private, nonprofit research and education institution dedicated to exploring molecular biology and genetics in order to advance the understanding and ability to diagnose and treat cancers, neurological diseases and other causes of human suffering.
Cold Spring Harbor Laboratory
Heterochromatin Current Events and Heterochromatin News RSSMassive project reveals shortcomings of modern genome analysis
The sequencing and comparison of 12 fruit fly genomes -- the result of a massive collaboration of hundreds of scientists from more than 100 institutions in 16 countries -- has thrust forward researchers' understanding of fruit flies, a popular animal model in science.
Where Broken DNA is Repaired
Ionizing radiation, toxic chemicals, and other agents continually damage the body's DNA, threatening life and health: unrepaired DNA can lead to mutations, which in turn can lead to diseases like cancer.
St. Jude study yields secrets of chromosome movement
Investigators at St. Jude Children's Research Hospital have used the lowly yeast to gain insights into how a dividing human cell ensures that an identical set of chromosomes gets passed on to each new daughter cell.
Exploring the Dark Matter of the Genome
Not so long ago, the difficult-to-sequence, highly repetitive, gene-poor DNA found in regions of chromosomes known as heterochromatin was called "junk." Like dark matter in the universe, the true nature of heterochromatin was unknown.
Regulating the Nuclear Architecture of the Cell
An organelle called the nucleolus resides deep within the cell nucleus and performs one of the cell's most critical functions: it manufactures ribosomes, the molecular machines that convert the genetic information carried by messenger RNA into proteins that do the work of life.
Scripps research team reverses Friedreich's ataxia defect in cell culture
In the new study, the researchers tested a variety of compounds that inhibited a class of enzymes known as histone deacetylases in a cell line derived from blood cells from a Fredreich's ataxia sufferer.
Zeroing in on progeria: How mutant lamins cause premature aging
Children diagnosed with Hutchinson-Gilford Progeria Syndrome (HGPS) race through life against an unfairly fast clock. Cases are extremely rare-one in 8 million births-but time plays cruel tricks on HGPS newborns.
Retrovirus Invasion in Primate Evolution; Limiting the Transmission of Rabies: Press Release from PLoS Biology
The Chimp Genome Reveals Retroviral Invasions in Primate Evolution It's been known for a long time that only 2% - 3% of human DNA codes for proteins. Much of the rest of our genomes - often referred to as junk DNA - consists of retroelements, some of which can occasionally replicate and move to a new location in the genome.
More Heterochromatin Current Events and Heterochromatin News Articles
 | Heterochromatin: Molecular and Structural Aspects Ram Verma has assembled ten distinguished contributors to survey what is currently known about the relationship of the structure of DNA to its role in the function and expression of genes. The crucial role of heterochromatin in the organization of chromosomes is thoroughly explored in this resulting landmark edited volume. Cytogeneticists and other geneticists, molecular biologists, cytologists,... |
 | Silencing, Heterochromatin and DNA Double Strand Break Repair by Kevin D. Mills The field of DNA repair is vast and advancing rapidly. Silencing, Heterochromatin and DNA Double Strand Break Repair probes the relationship of DNA break repair and silent heterochromatin, using budding yeast as a model. The primary research presented in this book represents some of the most important work in this new field of... |
| Can variants in the constitutive heterochromatin of human chromosomes be detected consistently? by Michelle F Browner | |
| Polytene chromosomes, heterochromatin, and position effect variegation (Advances in genetics) by I. F Zhimulëv | |
 | Protein Complexes that Modify Chromatin. Current Topics in Microbiology and Immunology, No. 274 This book provides timely reviews of several protein complexes that regulate gene expression and chromatin dynamics. Examples of such complexes include: nucleosome assembly complexes, ATP-dependent chromatin remodeling complexes, histone acetyltransferase complexes, histone deacetylase complexes, heterochromatin complexes, SMC complexes and transcription elongation complexes. These chapters will... |
 | RNA Interference (Current Topics in Microbiology and Immunology) (Current Topics in Microbiology and Immunology) In the last few years the major effect that RNAi has had in invertebrate systems like C.elegans and drosophila is beginning to take hold in mammalian systems through both single gene knockdown experiments and genome-scale screens. In the next decade, there will no doubt be both notable successes and failures as we attempt to apply this genetic tool to various biological problems for the first... |
| Geterokhromatin i effekt polozheniia gena by I. F Zhimulev |
| © 2008 BrightSurf.com |