Epigenetics in Focus at Nature Reviews Genetics


Warning: Creating default object from empty value in /home/epigenet/public_html/wp-includes/functions.php on line 431

Following closely on the heels of the special issue of Cell on epigenetics, Nature Reviews Genetics today published its own focus issue on epigenetics (April 2007), with reviews from some of the most prominent experts in several sub-disciplines within epigenetics, including stem cell research, cancer epigenomics, and environmental epigenetics. The editors of the journal open the issue with a brief introduction:

The explosion of interest in epigenetics over the past few years has had an impact on many branches of genetic and genomic research. One of the hottest topics in the field of gene regulation relates to the role of epigenetic modifications in dictating the expression output of the genome. In genomics, the advent of technologies for the large-scale profiling of these marks has made the characterization of epigenomes a coveted goal. And chromosome biologists are increasingly learning how epigenetic modifications contribute to the structural packaging of the genetic material at various levels.

The cover of the issue, pictured below, is a cartoon sketchboard by the journal’s art editor, Patrick Morgan.

The issue is packed with five reviews on epigenetics topics of interest:

  • Environmental epigenomics and disease susceptibility by Jirtle RL and Skinner MK. Epigenetic modifications provide a possible link between the environment and disease-causing alterations in gene expression. Evidence from animal studies increasingly supports this theory, including recent findings of epigenetically mediated transgenerational alterations in phenotype that are caused by environmental exposure. Link
  • Epigenetic signatures of stem-cell identity by Spivakov M and Fisher AG. How do stem cells keep the genes that drive differentiation in a repressed state, while maintaining the ability to express them in the future? Increasing evidence indicates that distinctive epigenetic traits underlie this unique aspect of stem-cell biology. Link
  • Transposable elements and the epigenetic regulation of the genome by Slotkin RK and Martienssen R. Cells use a range of increasingly well understood epigenetic mechanisms to keep transposable elements under control. These silencing mechanisms have been co-opted during the course of evolution to contribute to key aspects of chromosome biology and gene regulation. Link
  • Cancer epigenomics: DNA methylomes and histone-modification maps by Esteller M. Recent technological advances allow epigenetic alterations in cancer to be studied across the whole genome. These approaches are being used to answer key outstanding questions about cancer biology, and to provide new avenues for diagnostics, prognostics and therapy. Link
  • The epigenetic regulation of mammalian telomeres by Blasco MA. Epigenetic modifications are key players in the regulation of fly and yeast telomeres, and recent studies indicate that the same applies in mammalian cells. These findings have implications for our understanding of the roles of telomeres in ageing and cancer. Link

The recent surge of coverage by high impact journals in the area of epigenetics likely reflects the major advances and discoveries made in recent years, and will hopefully provide renewed interest among scientists, funding bodies, and most importantly, the general public.

Agenda for March 2007 SACGHS Meeting Now Available


Warning: Creating default object from empty value in /home/epigenet/public_html/wp-includes/functions.php on line 431

The final agenda is now available online for the 12th meeting of the Secretary’s Advisory Committee on Genetics, Health, and Society, which will be held Monday, March 26th and Tuesday, March 27th in Adelphi, MD. This is the committee that earlier this year completed its report on the viability of a large population cohort study in the U.S. that was originally proposed by Francis Collins, director of the National Human Genome Research Institute.

The agenda for this month’s meeting does not seem to include any new information pertaining to the large population study. However, the agenda does include a briefing on the status of the Genetic Information Nondiscrimination Act, a session on the oversight of genetic testing, a session on gene patents and licensing practices, and proposals for new SACGHS study priorities. The two-day event will be webcast live on the web, and an archive of the webcast will be available shortly after its conclusion. Link

Attending Northwest Reproductive Sciences Symposium


Warning: Creating default object from empty value in /home/epigenet/public_html/wp-includes/functions.php on line 431

Today I am attending the 9th Annual Northwest Reproductive Sciences Symposium in Moscow, ID, hosted by the Center for Reproductive Biology at Washington State University and University of Idaho. I have just returned from attending the keynote presentation by Dr. Peter Donovan of the University of California, Irvine entitled “Making Stem Cells from Germ Cells and Germ Cells from Stem Cells.” I will post some of my notes from the presentation later tonight, and other upcoming talks may also be covered. Link

10 Best Ways to Save Time at the Lab Bench


Warning: Creating default object from empty value in /home/epigenet/public_html/wp-includes/functions.php on line 431

I’ve been working in research labs for the past 3+ years now. During that time, I’ve picked up on some great ways to save time when working at the bench. Here’s my 10 best tips:

1. Don’t Make It, Steal It. If you don’t have a reagent already made for your procedure, “borrow” it from the person next to you. Either put it back afterwards or make a new label for it with your name or initials.

2. Make Your Reagents Thief Proof. So if you actually went through the trouble of making your own reagent, don’t let your lab mates take advantage of your time investment. Place ambiguous labels on bottles so others have no idea what is really in the bottle. For reagents with a distinctive color or appearance, don’t use a clear bottle. It can also help to hide the most likely stolen reagents in the back of your reagent shelf.

3. Don’t Break for the Phone. I work in a lab shared by 5-6 people, and there is one phone where calls come in. Trust me, if you sit there long enough, someone else will get the phone, even if you’re closest. Be extra mindful of this and make sure to claim a bench as far from the phone as possible. If you’re already stuck in a bad spot, come up with a clever reason to have the phone moved to another location.

4. Take Advantage of Friendly People. If you have to head to another room or even to the refrigerator to pick something up, watch for someone else heading out of the lab or in the vicinity of the refrigerator. Ask them if they will grab X for you while they’re going. This is a real time saver and your “friend” will take this as a compliment that you trust them with your reagents.

Another tactic is to use the pity approach. Say you need a couple boxes of pipette tips for your assay, but they’re all the way across the lab. You have a quarter full box of tips on your bench. Using a subtle nudge, send your tips tumbling to the floor. “Oh [expletive], I dropped all my tips! Can someone grab me a couple boxes, please!?” This one is money.

5. Protect Your Investment. You’ve invested a lot of time into a procedure, so don’t get greedy with your time and hand it off midway to an undergraduate or technician. If you want it done right, do it yourself. Even a foolproof, any-dummy-can-do-this assay can be screwed up by the most experienced of technicians.

6. Eliminate Extra Distractions. Put yourself in a position to get things done with the least amount of distraction possible. Whether this means turning off the cell phone, shutting down the e-mail program, or putting a “Do Not Disturb” sign on your door, think of ways to eliminate those pesky interruptions. It can also be very helpful to work when others are not around — early mornings, late evenings, weekends, holidays.

7. Safety Is for Losers. You don’t need gloves for most things — just don’t bother. And if you have to wear them, don’t take them carefully off to save for after your lunch break. Toss them quickly and just grab new ones when you get back.

8. Make Your Things Exclusive. Are there things in your lab that are routinely shared between benches? It’s time to make them yours. Apply a brightly colored label to the item with your name and hide it in a secret drawer. This way you won’t have to go searching for it all the time when you need it. Don’t worry about others getting angry searching for it — your lab manager will eventually break down and get a new one.

9. Delegate Simple Tasks to Other People. So you weren’t lucky enough to find someone leaving the lab when you needed the reagent from across the hall. Just tell someone else to do it, particularly someone on their break or with less degrees than you. After awhile, they’ll understand that you’re busier than they are, and they should give you a hand.

10. Barter for Help. So you still can’t find free labor to help with your work? It’s time to get creative. Work out deals with your lab mates. “If you help me today, I’ll help you tomorrow.” Then make sure to reneg on the agreement.

Do you have some tips for saving time at the bench? Share yours in the comments.

Advertisement: File for your tax refund and have money in 24 hours.

DNA Methylation Involved in Memory Formation


Warning: Creating default object from empty value in /home/epigenet/public_html/wp-includes/functions.php on line 431

Researchers at the University of Alabama at Birmingham have published new research supporting their hypothesis that DNA methylation plays a role in forming memories (1). The link between methylation and memory formation came about from the observation that methylation was disregulated in people suffering from brain disorders such as autism and schizophrenia.

In their experiments, the researchers created fearful memories in rats by placing them in specific training chambers that gave them a mild shock. They could then test whether the rat remembered the shock by observing if the rat froze when placed in the same chamber.

The researchers used methylation inhibitors to discover that DNA methylation directly controlled the activity of genes known to either suppress or promote memory formation.

“To our knowledge, this study is the first to present evidence that DNA methylation, once thought to be a static process after cellular differentiation, is not only dynamically regulated in the adult nervous system but also plays an integral role in memory formation,” concluded Miller and Sweatt. They wrote that their findings indicate that DNA methylation has been co-opted by the central nervous system as a “crucial step” in regulating gene activity involved in memory formation.

The study is available in the March 15, 2007 edition of the journal Neuron. Link

References:

Miller CA and Sweatt JD. 2007. Covalent modification of DNA regulates memory formation. Neuron 53:857-869.
DOI 10.1016/j.neuron.2007.02.022.

Advertisement: Get 15 Complimentary Ringtones Now!

Epigenetics Attracting Attention from Investors


Warning: Creating default object from empty value in /home/epigenet/public_html/wp-includes/functions.php on line 431

I’ve talked before about e-mails I commonly receive from consultants, investors, and others regarding investment ideas of companies that are poised to take advantage of the research being done in epigenetics. I thought I would share a recent example of one such e-mail:

Hello Trevor-


Congrats on getting this site up. I first read about epigenetics in Discover magazine last year. It’s very interesting and intuitively seems more correct than “traditional” ideas about evolution. It’s a relief to have research that would validate the rise of cancers and “DNA gone mad” accumulated from the many internal and external toxins we have exposed ourselves to in just the past 3 (or so) generations.

This brings a sense of continuity and a more holistic element into our ultra individualistic society.

Keep up the good work.

On a side – I am also a student looking to pay my way through school. Given the emerging research and application of epigenetic research – I would like to invest in a company or research institute that will be applying the advancements to the marketplace. Would you have any advice for me as to where I can look for who is using the information and how? Would you suggest pharmaceutical company websites?

Now, here was my response:

Thank you for the comments. I am also very excited about the advancements being made through our growing understanding of epigenetic processes and our potential to understand more about cancers and diseases that have become prevalent over the past several generations. I like to point out to readers that I am literally learning about all of this just as you are — I had not taken a single genetics course when I started this site and thus my understanding of the methodologies used to increase our understanding of epigenetics was limited.

Regarding investments in companies that are applying these advancements to the marketplace, two companies I would look into are Epigenomics and MethylGene. Both companies are using publicly and privately funded research advancements to develop clinical tests and other marketable products. I have to also say that I am not an investment manager or expert and these should not be taken as endorsements of investments in these companies. I have no investment in either company nor any interest in suggesting that others invest in these companies. These are merely two companies that I know of that are ” applying the advancements to the marketplace.”

I hope this was helpful and I hope you continue to enjoy our coverage at Epigenetics News.

Trevor

It’s clear that investors are taking an active interest in epigenetics as a field that will shape market advances in the coming years.

Liposuctioned Fat as a Source of Stem Cells


Warning: Creating default object from empty value in /home/epigenet/public_html/wp-includes/functions.php on line 431

In 2004, members of the American Society of Plastic Surgerons performed over 320,000 liposuction procedures (1). Who knew that the extracted fat was a potential source of stem cells for research or therapeutics.

Dr. Philipe Collas at the University os Oslo in Norway is conducting research to identify the stem cells among liposuctioned fat cells that are the best at regenerating tissue.

“Fat tissue is an underappreciated source of stem cells,” Collas pointed out. Unlike other sources of adult stem cells, such as bone marrow, fat is abundant and there is no shortage of donors. “It’s wonderful, we have litres and litres of material from cosmetic surgery clinics and end up with bucketfuls of stem cells to work with,” he notes.

Researchers ackowledge that the key to transforming adult stem cells from fat into other cell types is in their epigenetic signature, such as the level of methylation.

Epigenetic marks contribute to switching genes on and off, and stem cells rely on them heavily as they divide and mature. The Oslo team has found that low rates of DNA methylation, for instance, boost the chances of transforming fat stem cells from one cell type into another. “Look at a cell’s epigenetic profile,” says Collas, “and you may be able to predict what that cell is likely to turn into.”

These epigenetic signatures have grabbed everyone’s attention, acknowledges Ernest Arenas, a EuroSTELLS researcher at the Karolinska Institute in Stockholm, Sweden. “Scientists in the stem cell field are starting to realise that for cell manipulations to succeed they need to pay attention to their epigenetic marks. Cells can’t be pushed along to become a different cell type unless they start out with the right set of [epigenetic] conditions.”

Epigenetics remains one of the most promising avenues of research for identifying ways to differentiate plentiful adult stem cells into other cell types for therapeutic purposes. Link

Potential Conflict of Interest at NIEHS


Warning: Creating default object from empty value in /home/epigenet/public_html/wp-includes/functions.php on line 431

The National Institutes of Environmental Health Sciences (NIEHS) is under fire. Effect Measure, a blog written anonymously by public health experts and practitioners, has written a critical review of David Schwartz’s two year term as director of the NIEHS:

Schwartz, like other Bush appointees, has a penchant for outsourcing public functions to private concerns, and under his boss, NIH Director Elias Zerhouni, even the peer review function was put out for bids. Schwartz has been dismantling the flagship environmental health scientific journal, Environmental Health Perspectives (EHP), moving to outsource it, gut its news and comment sections and eliminate the foreign language editions. EHP is an open access journal, but if it is outsourced it may not remain that way. The biggest losers are the many scientists in the developing world, whose environmental problems dwarf those in the developed world. Schwartz had given his word that EHP would not be privatized, an assurance forced on him by congressional pressure. But one of the most disheartening aspects of his reign is that his word cannot be relied upon. Link

The comments from Effect Measure were primed by an article in the LA Times indicating that Sciences International, a private consulting firm, is being questioned by Congress regarding its role as an advisor to the NIEHS and potential conflicts of interest. The potential conflict of interest in question is that in 2006, Sciences International had clients that were among the largest names in the chemical industry, which produces compounds that have been shown to be damaging to reproductive health.

“The most significant project at our firm is the management of the National Toxicology Program’s Center for the Evaluation of Risks to Human Reproduction,” the Sciences International website says. It says half its clients are from the private sector, but its health studies are independent and it “is proud of its reputation for objective science.”

Its current website contains no list of industry clients. But a 2006 version names BASF and Dow Chemical — which manufacture the plastics compound BPA — as well as DuPont, Chevron, ExxonMobil, 3-M, Union Carbide, the National Assn. of Manufacturers, and 45 other manufacturing companies and industry groups.

In 1999, Sciences International represented R.J. Reynolds Tobacco Co. in fighting an Environmental Protection Agency proposal to regulate a pesticide used on tobacco crops. In 2004, its vice president, Dr. Anthony Scialli, who is identified as the federal center’s “principal investigator,” co-wrote a study with a Dow Chemical Co. researcher on how to extrapolate data from animal tests to humans.

In addition, another Sciences International employee who works at the federal agency, Gloria Jahnke, has collaborated nine times on chemicals research with another company that gets funding from the plastics industry, according to a Times review of medical publications. Link

Director David Schwartz has written letters in the past indicating his support of epigenetics research, and his 5-year plan for the agency highlighted epigenetics as an important avenue of investigation.

Update: Additional information on Sciences International and the debate on “privatizing science” is available at The Pump Handle, a relatively new blog on public health. The article is written by Dr. David Michaels, who heads the Project on Scientific Knowledge and Public Policy (SKAPP) and is Professor and Associate Chairman in the Department of Environmental and Occupational Health, the George Washington University School of Public Health and Health Services. Link

The New Look


Warning: Creating default object from empty value in /home/epigenet/public_html/wp-includes/functions.php on line 431

I went and did it: Epigenetics News now has a brand new look. I am still working out the kinks, but this design should load much faster and is much more “simple” than the previous rendition. I hope that the readability is still very good (or better) and that the appearance doesn’t detract from the content.

If you’re reading from the RSS feed, you may want to click through to find out what the new site looks like and leave your two cents. Link

Epigenetics Symposium a Success at University of Arizona


Warning: Creating default object from empty value in /home/epigenet/public_html/wp-includes/functions.php on line 431

The Arizona Daily Wildcat reports on the first major science symposium held last Saturday in the new Thomas W. Keating Bioresearch building at the University of Arizona in Tucson: Epigenetic Control of Gene Expression and Inheritance Symposium.

    Maureen Peterson, a first-year genetics graduate student, said because of the symposium, she wants to do further research in epigenetics, which she explained as the difference in gene expression levels that occur from modifications of the DNA molecule, not on changes of the DNA sequence itself.

    In the last five to 10 years, the additional mechanisms superimposed upon the underlying DNA sequence that form the genetic basis of the template of gene regulation have become the focus for scientists, said Vicki Chandler, director of the BIO5 Institute and a professor of plant sciences and molecular and cellular biology.

The symposium was attended by about 120 researchers and students. Speakers included Thomas Jenuwein, Steven Henikoff, Richard Amasino, Danesh Moazed, Anne Ferguson-Smith, Vicki Chandler, and Arturas Petronis. Link

New Mendel’s Garden Now Available


Warning: Creating default object from empty value in /home/epigenet/public_html/wp-includes/functions.php on line 431

The latest edition of Mendel’s Garden, the blog carnival devoted to all things genetic, is now available at Behavioral Ecology Blog. Among the highlights this week are posts on the genetics of ABO blood types and eye color, the keys to managing DNA sequencing data, and details of the pitfalls in amassing large DNA databases. Link

Gadd45a Promotes Epigenetic Gene Activation by Repair-Mediated DNA Demethylation


Warning: Creating default object from empty value in /home/epigenet/public_html/wp-includes/functions.php on line 431

Nature has published a letter from researchers at the German Cancer Research Center involving their implication of the gene Gadd45a in one of the black boxes of epigenetic mechanisms: demethylation.

DNA methylation is an epigenetic modification that is essential for gene silencing and genome stability in many organisms. Although methyltransferases that promote DNA methylation are well characterized, the molecular mechanism underlying active DNA demethylation is poorly understood and controversial. Here we show that Gadd45a (growth arrest and DNA-damage-inducible protein 45 alpha), a nuclear protein involved in maintenance of genomic stability, DNA repair and suppression of cell growth, has a key role in active DNA demethylation. Gadd45a overexpression activates methylation-silenced reporter plasmids and promotes global DNA demethylation. Gadd45a knockdown silences gene expression and leads to DNA hypermethylation. During active demethylation of oct4 in Xenopus laevis oocytes, Gadd45a is specifically recruited to the site of demethylation. Active demethylation occurs by DNA repair and Gadd45a interacts with and requires the DNA repair endonuclease XPG. We conclude that Gadd45a relieves epigenetic gene silencing by promoting DNA repair, which erases methylation marks.

Link

One of the experiments from this paper seem to support the recent finding that demethylation of the proximal-promoter region is required for active transcription.

ScienceDaily offers a summary of this research adapted from a press release from the German Cancer Research Center. Link

Science Links for the Weekend


Warning: Creating default object from empty value in /home/epigenet/public_html/wp-includes/functions.php on line 431

Here’s some of the best science links I’ve come across over the past couple weeks:

  • Volunteers at LibriVox have created a free audiobook of Charles Darwin’s On the Origin of Species by Means of Natural Selection (1859). Total running time: 24:22:37, total download size: 702.2 MB. (HT: Boing Boing).

  • Neurotopia hosts the 74th edition of Tangled Bank, which offers some of the best science writing from around the blogosphere over the past couple weeks.
  • Migrations brought my attention to an excellent cell biology animation with a voiceover explaining the processes you are seeing illustrated. If you do any cell biology teaching, this may be a great video to play in your class.
  • You may feel like you’re underpaid. This New York Times article provides Web sites that offer information on average salaries based on job title and description, education, and experience. If you happen to work at Washington State University, you can peruse the salaries of any non-student employee at Cougster, which obtained the information using a public information request (click Cougster Files, then WSU Pay). I’ve talked before about tips for getting employed as an undergraduate researcher.

The Big Commercial Break and An Idea


Warning: Creating default object from empty value in /home/epigenet/public_html/wp-includes/functions.php on line 431

In the last week, two more sponsors have chosen to purchase a text link at Epigenetics News: Surgeon’s Advisor and HealthTalk.

Surgeon’s Advisor is a marketing firm that asists cosmetic surgeons, plastic surgeons, and doctors increase their visibility on the web through search engine optimization (SEO), site design, link building, and other techniques. If you’re a medical professional looking to increase your Internet visibility and build clients, check out Surgeon’s Advisor. Link

HealthTalk is a sensibly designed web site offfering information and resources for various diseases, including Alzheimer’s/dementia, Crohn’s disease, multiple sclerosis, and rheumatoid arthritis. The site offers scheduled webcasts and teleconferences with doctors discussing therapy options, and a host of blogs devoted to sharing advice and experiences for those that live with or with people that suffer from these diseases. Link

Now, on to the big idea: I am seriously contemplating changing the theme of Epigenetics News. I chose the Ocadia theme because it offered a professional look and subtle tones, which I like. But the downside is that the theme has a number of graphics that cause slow loading, especially on the home page.

Now, this will probably come as a surprise to the majority of our readers, because site statistics indicate that the majority of Epigenetics News readers are on broadband connections — undoubtedly lots of university and corporate connections. But I know how slow it actually is because until a few months ago, I was stuck with dial-up access from home.

I think that perhaps changing themes will offer the opportunity for faster page loads, a fresh new look, and encourage new visitors on slower connections to stick around. If you have any comments on the current theme or things you’d like to see stay or go, respond in the comments.

Need Help in the Lab? Just Hit the Forums


Warning: Creating default object from empty value in /home/epigenet/public_html/wp-includes/functions.php on line 431

I recently got word that there is an active forum available for researchers in epigenetics; mainly DNA methylation and chromatin modification experiments. Protocol Online maintains a DNA Methylation, Histone and Chromatin Study forum that is fairly active. The majority of the posts seem to deal with bouncing ideas between technicians for troubleshooting problems in common assays such as bisulfite conversion and ChIP assays. This could be a lifesaver for a graduate student or technician looking for assistance in troubleshooting problems with an assay.

Most importantly, these forums provide anonmyity for the participants to allow for seeking advice on simple protocol troubleshooting issues. These kinds of active forums are hard to come by, and one specific for epigenetics researchers could be a helpful resource for many of our busy readers. Link