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.
Genes That Control Embryonic Stem Cell Fate Identified Print E-mail
Science - Genetics & Genome
TS-Si News Service   
Sunday, 13 July 2008 17:00
RNA interference (RNAi) is a mechanism that inhibits gene expression at the stage of translation or by hindering the transcription of specific genes.
TS-Si Genetics & The Genome
Montreal, Quebec, CAN. Life on Earth didn't originate from a preexisting blueprint, but living things do have a basic architecture. Recent studies have shown that a great deal of the genome — inluding the non-coded (&q...
St. Louis, MO, USA. For years, scientists have struggled to decipher the genetic instruction book that details where and when the 20,000 genes in a human cell will be turned on or off. Different genes operate in each cell typ...
Los Angeles, CA, USA. Scientists have demonstrated for the first time the reversal of what is called epigenetic silencing, a major breakthrough in the developmental process.   Although nearly every cell in our body is ...
Edmonton, Alberta, Canada. People are different, both physically and mentally, but genetically everyone is very similar. That's been the thought of scientists for decades now. But with population research becoming more and mo...
Melbourne, Victoria, AUS. Scientists have identified a significant DNA variation that they say could result in a genetic link between reduced testosterone action and male-to-female (MtF) transsexualism (progressively known as...
Oxford, UK. What do you look for in a mate? Or, does it even matter if you look? Past discussions of mate selection have been dominated by arguments based on the evidence of nurture. For example, the exam...
Atlanta, GA, USA. There was a time when books were reproduced by hand, a laborious procedure that is subject to errors and confused readers. Cells have a more daunting task, since their division must result in an identic...
Oslo, Norway. Ask this basic question to the next 10 people you meet at random: What is a gene? Chances are that most of the answers will either reflect a dated understanding of science or ignore science altog...
San Franciso, CA, USA. Scientists have identified about two dozen genes that control embryonic stem cell fate. The genes may either prod or restrain stem cells from drifting into a kind of limbo, they suspect. The limbo lies between the embryonic stage and fully differentiated, or specialized, cells, such as bone, muscle or fat.
 
The new findings come from the first large-scale search for genes crucial to embryonic stem cells. The research was carried out by a team at the University of California, San Francisco (UCSF) and reported in the journal Cell.
 
An RNAi Screen of Chromatin Proteins Identifies Tip60-p400 as a Regulator of Embryonic Stem Cell Identity. Thomas G. Fazzio, Jason T. Huff, and Barbara Panning. Cell 134 162-174.
 
By knowing the genes and proteins that control a cell's progress toward the differentiated form, researchers may be able to accelerate the process. There are important potential benefits from the finding: a better understanding of how cell differentiation affects the prevalence of birth conditions, the study of some degenerative diseases, or the use of stem cells in therapy.
 
Barbara Panning, PhD, associate professor of biochemistry and biophysics at UCSF.
 
Barbara Panning, PhD, is a UCSF associate professor of biochemistry and biophysics, and the paper's senior author. She has done foundational research on decipherig commands that control the X chromosome shutdowns in the cells of every human female. Photo by Robert Foothorap.
 
 
"The genes we identified are necessary for embryonic stem cells to maintain a memory of who they are," says Panning. "Without them the cell doesn't know whether it should remain a stem cell or differentiate into a specialized cell."
 
The scientists used a powerful technique known as RNA interference, or RNAi, to screen more than 1,000 genes for their role in mouse embryonic stem cells. RNAi is a gene-silencing process that inhibits gene expression by causing the degradation of specific RNA molecules or hindering the transcription of specific genes. The technique allows researchers to "knock down" individual genes, reducing their abundance in order to determine the gene's normal role.
 
RNAi Process.
 
The RNAi Process. Small RNA molecules activate a cellular response to destroy a specific mRNA.
 
Image courtesy of Richard Robinson; adapted under a Creative Commons Attribution License.
 
 
Source: RNAi Therapeutics: How Likely, How Soon? Richard Robinson PLoS Biology 2(1) e28 doi: 10.1371/ journal.pbio.0020028
 
 
The research focused on proteins that help package DNA. In the nucleus, DNA normally wraps around protein complexes called nucleosomes, forming a structure known as chromatin. This is what makes up chromosomes.
 
They found 22 proteins, each of which is essential for embryonic stem cells to
  • maintain their consistent shape,
     
  • growth properties, and
     
  • pattern of gene expression.
Most of the genes code for multi-protein complexes that physically rearrange, or "remodel" nucleosomes, changing the likelihood that the underlying genes will be expressed to make proteins.
 
The main player they identified is a 17-protein complex called Tip60-p400. This complex is necessary for the cellular memory that maintains embryonic stem cell identity, Panning explains. Without it, the embryonic stem cells turned into a different cell type, which had some features of a stem cell but many features of a differentiated cell.
 
The scientists believe that Tip60-p400 is necessary for embryonic stem cells to correctly read the signals that determine cell type. These findings are not only important for understanding cellular memory in embryonic stem cells, but will also likely be relevant to other cell types, they say.
 
Inactivation of other genes disrupted embryonic stem cell proliferation. These genes were already known to have only slight influence on viability of mature cells in the body. This suggests that embryonic stem cells are "uniquely sensitive to certain perturbations of chromatin structure," the scientists report.
 
If other types of stem cells are also found to be sensitive to these chromatin perturbations, this could lead to novel cancer therapies in the future, Panning says.
 


Lead author on the paper is Thomas G. Fazzio, PhD, a postdoctoral fellow. Co-author is Jason T. Huff, BSc, a graduate student. Both are in Barbara Panning's lab.

The research is supported by the US National Institutes of Health (NIH).

 


An RNAi Screen of Chromatin Proteins Identifies Tip60-p400 as a Regulator of Embryonic Stem Cell Identity. Thomas G. Fazzio, Jason T. Huff, and Barbara Panning. Cell 134 162-174.

Summary

Proper regulation of chromatin structure is necessary for the maintenance of cell type-specific gene expression patterns. The embryonic stem cell (ESC) expression pattern governs self-renewal and pluripotency. Here, we present an RNAi screen in mouse ESCs of 1008 loci encoding chromatin proteins. We identified 68 proteins that exhibit diverse phenotypes upon knockdown (KD), including seven subunits of the Tip60-p400 complex. Phenotypic analyses revealed that Tip60-p400 is necessary to maintain characteristic features of ESCs. We show that p400 localization to the promoters of both silent and active genes is dependent upon histone H3 lysine 4 trimethylation (H3K4me3). Furthermore, the Tip60-p400 KD gene expression profile is enriched for developmental regulators and significantly overlaps with that of the transcription factor Nanog. Depletion of Nanog reduces p400 binding to target promoters without affecting H3K4me3 levels. Together, these data indicate that Tip60-p400 integrates signals from Nanog and H3K4me3 to regulate gene expression in ESCs.

 
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 Sunday, 13 July 2008 17:26