How Often is the Word ‘Epigenetics’ Used? More Than Ever.


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There has been some discussion as of late concerning the increasing use of the words “epigenetic” and “epigenetics.” For starters, amnestic at Gene Expression wrote an excellent two-part series on epigenetics and memory (part 1, part 2) that included a review of definitions of epigenetics and some discussion concerning use of the word.Earlier this month, Mark Ptashne of the Sloan Kettering Institute in New York wrote an essay in the journal Current Biology on the use of the word “epigenetic.” Link

Over the past few years we have seen an odd change, or extension, in the use of the word ‘epigenetic’ when describing matters of gene regulation in eukaryotes. Although it may generally be that it is not worth arguing over definitions, this is true only insofar as the participants in the discussion know what each other means. I believe the altered use of the term carries baggage from the standard definition that can have misleading implications. Here I wish to probe our use of language in this way, and to show how such a discussion leads to some more general considerations concerning gene regulation.

The essay goes on to describe how certain regulators of gene expression now commonly referred to as “epigenetic modifications” are perhaps improperly labelled because these changes are not heritable.I went ahead and did a review of the publications listed at PubMed tha contain the word “epigenetics” from 2000 to 2006. Here are the results:Epigenetics Publications by YearThe results show that there is clearly a significant increase in use of the word “epigenetics” in scientific publications over the past 7 years. Here are a few factors that I believe are the most likely contributors in an increase in use of the word, although I suspect that long-time researchers within the field may have a better grasp of other trends that have also contributed to its increasing popularity.

  • Advances in technologies to study epigenetic mechanisms.There have been considerable advances in technology that allow for the study of the influence that epigenetics has on many different areas of research. This is a great positive feedback loop: as better technology becomes available, more research is done, which drives development of better tools for researchers to use.
  • New insights into the link between epigenetics and cancer. Epigenetics (i.e. DNA methylation) has offered new hope for understanding how cancer develops and finding new ways to detect and diagnose it.
  • Surprising discoveries bring new researchers into the field. Some researchers stumbled into epigenetics research when their own, unrelated research led them down this path. Again, advances in technology to study epigenetics have largely made this possible.

The increase in the popularity of epigenetics has emerged earlier this year in the form of two high impact journals, Cell and Nature Reviews Genetics, publishing special editions solely on new topics in the epigenetics field. And last year an entire textbook on epigenetics was published by Cold Spring Harbor Press, indicating that the field has grown to a level that warrants such special attention.It’s also important to note that stem cell researchers are increasingly becoming interested in how epigenetics may hold the key for critical advances in their understanding of these unique cell types. And epigenetics is now clearly important in improving the efficiency of cloning (somatic cell nuclear transfer), which will be tremendously beneficial to a wide spectrum of researchers and most importantly, to public health.With all of these high profile and highly funded areas becoming closely associated with epigenetics, is it any surprise that more researchers are finding ways to include their focus as part of “epigenetics”?

Grant Writing: Does It Get Any Better?


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I’ve been taking a graduate course this semester, “Molecular and Cellular Reproduction,” that aims to provide a comprehensive overview of all of the most relevant areas of reproductive biology from a physological, molecular, and cellular perspective. It’s been informative and fascinating, and as an undergraduate taking a completely unrequired course, it’s been challenging at times to remain engaged when other (required) courses demand my time.

However, recently I’ve been working on one of the course’s main requirements: a 5-10 page grant application that will conclude with an NIH style review session. This will allow all members of the class to get practical and objective review of their grant (whether it will be submitted or not) and hopefully provide an opportunity to improve our understanding of how to construct a quality grant application more likely to be funded.

And I’ve got to say: I love this stuff.

Writing this grant has been one of the few things in my undergraduate career that has provided a natural progression of ideas and revisions, and slowly working to a quality finished project. Undergraduate science courses provide so few opportunities for creative thought and association of disparate ideas that you tend to start stumbling along as if in a daze. Learn some basic concepts, memorize more concepts and mechanisms, recite and draw facts and figures for exams and quizzes, rinse and repeat.

But this grant is something unique, something closely related to the research I’ve poured countless hours into over the past 2.5 years. It requires careful crafting and thoughtful analysis of the best way to present an idea to a group of young graduate students. It requires major and minor revisions at each step along the way as a garbled early draft slowly transforms into something much more refined.

I’m not saying that I’m good at it yet — far from it. But I do like the process, and it has helped cement my decision to head for graduate school following graduation in May 2008.

Mammal-Specific Protein Associates with Male Chromatin, Required for Male Meiosis


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A new paper available today in PLoS Genetics suggests that a mammal-specific protein (DMRT7) related to the invertebrate sexual regulators Doublesex and MAB-3 controls the transition from meiotic sex chromosome inactivation to postmeiotic sex chromatin in males (1).

Genes related to the sexual regulator Doublesex of Drosophila have been found to control sexual development in a wide variety of animals, ranging from roundworms to mammals. In this paper, we investigate the function of the Dmrt7 gene, one of seven related genes in the mouse. Female mammals are XX and males are XY, a chromosomal difference that presents specific challenges during the meiotic phase of male germ cell development. Some of these are thought to be overcome by incorporating the X and Y chromo- somes into a specialized structure called the XY body. We find that DMRT7 protein is present in germ cells, localizes to the male XY body during meiosis, and is essential for male but not female fertility. The XY body normally is altered by recruitment of additional proteins and by specific modifications to histone proteins between the pachytene and diplotene stages of meiosis, but modification of the “sex chromatin” in Dmrt7 mutant cells is abnormal during this period. Because Dmrt7 is found in all branches of mammals, but not in other vertebrates, these results may indicate some commonality in regulation of sex chromatin among the mammals.

References:

1. Kim S, Namekawa SH, Niswander LM, Ward JO, Lee JT, Bardwell VJ, Zarkower D. 2007. A mammal-specific Doublesex homolog associates with male sex chromatin and is required for male meiosis. PLoS Genetics 3(4): e62.
doi:10.1371/journal.pgen.0030062

Epigenetics Researcher C. David Allis Grabs Gairdner Award


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C. David Allis of The Rockefeller University is one of five scientists to receive a 2007 Gairdner International Award. Allis is recognized for his work on how histones affect genome stability and gene transcription. Each award winner receives US$30,000 and a statue at an award dinner to be held on October 25 in Toronto, Canada.

The “Gairdners,” founded by the late Toronto businessman, James Gairdner, are now in their 48th year. They have grown to be one of the most prestigious international awards for medical research, recognizing outstanding contributions by medical scientists worldwide whose work will significantly improve the quality of life. Of the 283 Gairdner awardees, 68 have gone on to win the Nobel Prize.

C. David Allis is also the editor of the epigenetics textbook released last year by Cold Spring Harbor Press. Link

Epigenomics & Sequencing Meeting 2007: July 9-10 in Boston, MA


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GeneExpression Systems, Inc. will be hosting the 1st International Epigenomics & Sequencing Meeting on July 9-10, 2007 at The Conference Center at Harvard Medical School in Boston, Massachusetts. I spoke with GeneExpression Systems Founder and CEO Dr. Krishnarao Appasani, who explained that the meeting is aimed at bringing together a diverse field of epigenomics researchers from both academia and industry. Key topics of the meeting will include mechanisms of chromatin in gene regulation, ChIP on ChIP and methylation assays, epigenetic reprogramming in stem cells, epigenome sequencing, and epigenetic regulatory processes in disease and environment.

Speakers at the meeting will include Rene Cortese of Epigenomics AG, Alex Meissner of The Whitehead Institute for Biomedical Research, and Christopher Adams of Invitrogen’s Epigenetics Division. If you would like to have a 25-minute speaking session at the meeting, there is still time to grab a spot. Additionally, poster abstracts will be accepted until June 10, 2007.

Registration for the meeting costs US$499 for academic/government, US$399 for students, and US$999 for commercial. Nearby hotel accomodations range from US$179 to US$199 per night. Link

Disclosure: Epigenetics News is a media sponsor of this meeting.

AACR 2007: SuperGen Showcases Selective Degradation of DNMT1


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At the 2007 annual meeting of the American Association for Cancer Research (AACR), pharmaceutical company SuperGen (NASDAQ:SUPG) presented data on a class of quinilone-based compounds that are not incorporated into DNA, selectively induce the degradation of DNA Methyltransferase I (DNMT1) in human cancer cells and re-express silenced tumor supressor genes.

Researchers have discovered a novel class of quinoline-based compounds that are not incorporated into DNA and cause selective degradation of DNMT1 in human cancer cells with minimal or no effects on DNMT3A and DNMT3B that have been discovered. This addresses an issue with re-activation of silenced tumor suppressor genes by 5-Azacytidine (5-AzaC or Vidaza) and its congener 5-aza- deoxycydinite (5-aza-CdR or Decitabine or Dacogen). These compounds provide a different mechanistic approach to the creation of cancer therapies because they selectively and rapidly induce degradation of maintenance DNA methyltransferase, DMNT1. However, they show some toxicity due to their incorporation into the cell DNA. One compound in particular, S1027, resulted in complete degradation of DNMT1 within 24 hours of treatments and also blocked degradation as a pre-treatment of cells with proteasomal inhibitors.

SuperGen also showcased their work showing that zebrafish provide an excellent screening model for small molecule inhibitors of DNMT1. Link

Submissions for Mendel’s Garden in May


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The genetic blog carnival Mendel’s Garden will be hosted here at Epigenetics News on Monday, May 7. Submissions of anything related to genetics, epigenetics, evo devo, regulation of gene expression, genetic counseling, ethical issues, or closely related topics will be accepted. Send your submissions to admin AT epigeneticsnews DOT com.

AACR 2007: Epigenomics Improving Colorectal Cancer Detection Success Rate


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Berlin- and Seattle-based Epigenomics AG has announced at the Annual Meeting 2007 of the American Association for Cancer Research (AACR) that it has significantly improved its success rate at detecting colorectal cancer by analyzing DNA methylation in blood serum. The increased success of detection was mediated by altering the assay procedure and rules for test result interpretation.

The poster presentation by Cathy Lofton-Day, Ph. D., Vice President Molecular Biology of Epigenomics, focused on the benefits of modifications of the assay procedure and rules for test result interpretation on the performance of Septin 9 for the early detection of colorectal cancer in blood plasma. Using these modifications Septin 9 detected 70% (91 out of 130) of the colorectal cancers in the study and was falsely positive in only 10% (19 out of 183) of the cancer-free controls. When specificity was set at 97% (3% false positive rate in the non-cancerous controls) 63% of cancers were reliably detected. More importantly, the 70% cancer detection rate was also achieved in individuals found to have earlier stage disease (stage I-III, 75 out of 107).

Epigenomics is now focusing on further streamlining and simplification of the assay procedure to decrease test costs, improve ease-of-use and thus facilitate transfer into clinical routine use.

The PDF of the poster presented by Dr. Lofton-Day is available at the Epigenomics web site.

In July 2006 Epigenomics announced that it had improved its colorectal cancer detection rate by using a Septin9 methylation assay in conjunction with a previously unidentified marker, ALX4. This new data seems to suggest that Epigenomics is now trying to improve detection through analysis of Septin9 alone, possibly to streamline the development of the assay for clinical use. Link

Sympathy for the Virginia Tech Community


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After a day to let the news sink in, the shootings on the campus of Virginia Tech University in Blacksboro, Virginia are on the minds of myself and many of my co-workers and fellow students at Washington State University. There is plenty of coverage of the tragedy online, including up-to-the-minite details available at CNN. The shootings were also on the minds of many of the science bloggers at Seed Magazine’s Scienceblogs.com, which was summarized by Dave Munger at Cognitive Daily.

From Dave Munger:

…this morning everyone rushed off to school and to work, and I started watching some of the online footage of the shootings. After a while I couldn’t think about anything else, so I began to look for distractions. As I should have known, the distractions just weren’t distracting enough, and I kept connecting everything back to the grisly deaths in Virginia.

From Janet Stemwedel at Adventures in Ethics and Science:

I’m still having trouble getting words to really wrap themselves around the immediate feeling of panic in my gut. College campuses have always felt like safe places to me, and relative to most other places you could be, I’ll bet statistically they really are pretty safe. But the Ivory Tower is still vulnerable to Very Bad Stuff.

From Jason Rosenhaus at EvolutionBlog:

I just spent the weekend at a local math conference that included quite a few faculty members and students from Tech. I made some new friends, and renewed some old aquaintances. I do not know if any of them were directly affected. It’s hard to imagine that after the high spirits and light mood of the conference, they had to go back to find this carnage. It’s sobering to be reminded that it only takes one crazy person to inflict this much damage.

In addition, earlier today outgoing Washington State University President V. Lane Rawlins offered his condolences to the Virginia Tech community:

We are all grieving over the tragic events that occurred yesterday at Virginia Tech. The senseless loss of lives is beyond comprehension. Many of us here know people who work, teach or study at Virginia Tech, so this is very much a shared tragedy. While there can be no absolute guarantees of safety in public spaces, this event should cause all of us to redouble our efforts to better understand how to prevent such acts in the future.

During the aftermath of what has happened, some people on our own WSU campuses may be anxious and concerned about safety as a result of those tragic and highly publicized actions. We are taking this time to review our own emergency response plans and to communicate key aspects of them to you.

It is important to emphasize that Washington State University has complete, up-to-date emergency preparedness and response plans for all four of our campuses and other university locations. Here are key points you all will want to know:

  • WSU has an emergency response plan that immediately notifies University leaders so that critical decisions can be made. The response plan has been tested through exercises with the executive team and the Council of Deans. Today I have asked all deans and vice presidents to schedule similar emergency response exercises promptly.
  • Our three regional campuses have emergency response plans relevant to their own settings, and those plans have been tested.
  • WSU has a system for immediately communicating to our community including faculty, staff and students through the WSU Alert emails and the companion WSU Alert Web site at http://www.alert.wsu.edu.
  • We are preparing to install a siren and loudspeaker system throughout the Pullman campus. We will propose that similar systems be installed at our campuses in Spokane, the Tri-Cities and Vancouver.

We believe that our campuses are among the safest in the nation. We also believe that we are well-prepared in case of emergencies, and we are reviewing and updating our plans on a continuous basis.

Equally important at this time is for us to be sensitive to the fears and concerns of those in our WSU community. We encourage that individuals and groups take advantage of opportunities for discussion and counseling. This is a time for all in the Cougar family to be mutually supportive. Thank you.

V. Lane Rawlins,
President

Illumina Launches Custom Methylation Application


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Today Illumina, Inc. (NASDAQ:ILMN) launched a custom-content methylation product that allows researchers to perform methylation profiling specific to individual CpG sites. From the press release:

Joining Illumina’s GoldenGate Methylation Cancer Panel I, the Company’s first standard methylation product launched in January 2007, investigators now have the option to select their favorite genes or gene regions to cost-effectively survey up to 1,536 methylation sites of choice across 96 samples simultaneously.

“Custom methylation adds another degree of integration to analysis with genetic and epigenetic data. Researchers who are interested in expediting the speed and scope of their methylation studies in areas such as cancer, developmental disorders, stem cell, aging, and neurological diseases now have the ability to select specific CpG sites from chosen genes” said Marina Bibikova, Ph.D., Staff Scientist at Illumina.

Link

Retrotransposon Silencing by DNA Methylation Can Drive Mammalian Imprinting


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A new article was published today in PLoS Genetics concerning mammalian genomic imprinting — specifically, in the marsupial tammar wallaby (Macropus eugenii) and the egg-laying platypus (Ornithorhynchus anatinus):

Among mammals, only eutherians and marsupials are viviparous and have genomic imprinting that leads to parent-of-origin-specific differential gene expression. We used comparative analysis to investigate the origin of genomic imprinting in mammals. PEG10 (paternally expressed 10) is a retrotransposon-derived imprinted gene that has an essential role for the formation of the placenta of the mouse. Here, we show that an orthologue of PEG10 exists in another therian mammal, the marsupial tammar wallaby (Macropus eugenii), but not in a prototherian mammal, the egg-laying platypus (Ornithorhynchus anatinus), suggesting its close relationship to the origin of placentation in therian mammals. We have discovered a hitherto missing link of the imprinting mechanism between eutherians and marsupials because tammar PEG10 is the first example of a differentially methylated region (DMR) associated with genomic imprinting in marsupials. Surprisingly, the marsupial DMR was strictly limited to the 5′ region of PEG10, unlike the eutherian DMR, which covers the promoter regions of both PEG10 and the adjacent imprinted gene SGCE. These results not only demonstrate a common origin of the DMR-associated imprinting mechanism in therian mammals but provide the first demonstration that DMR-associated genomic imprinting in eutherians can originate from the repression of exogenous DNA sequences and/or retrotransposons by DNA methylation.

The full text is available for free to the public. Link