How regulatory sequences evolve in fruit flies

An IMP-Brandeis collaboration reveals the evolution of regulatory sequences in Drosophilids

By Yuliya Sytnikova and Nelson Lau

Enhancers are cis-regulatory DNA sequences that influence the promoters of genes, but identifying enhancers is not a straightforward process. Previously, the Stark lab developed a method for genome-wide enhancer detection called STARR-seq, (Arnold, Gerlach et al. 2013), that allowed them to identify thousands of enhancer sequences around the Drosophila melanogaster genome. In the most recent issue of Nature Genetics, a collaboration between the Stark lab of the IMP (Institute of Molecular Pathology) in Vienna, Austria, and the Lau lab at Brandeis University examines this hypothesis by studying the conservation of enhancer regulatory regions during Drosophilid fly evolution.

To ask if enhancers from D. melanogaster enhancers are also conserved in other Drosophila species in their sequences and locations, the Stark lab extended the STARR-Seq approach to D.yakuba and D.ananassae, which are separated from D.melanogaster by 11 and 40 million years ago, respectively (Arnold, Gerlach et al. 2014). Interestingly, this study also revealed hundreds of new sequences that gained enhancer function differentially between D.yakuba, D.ananassae, and D.melanogaster.

However, to test if these new sequences meaningfully direct different gene expression changes, the Lau lab conducted a targeted mRNA profiling experiment in purified endogenous follicle cells from D.yakuba and D.ananassae. The Stark lab had initiated the STARR-Seq analysis in an Ovarian Somatic Cell (OSC) line, which originated from the follicle cells of D.melanogaster, therefore the profiling of endogenous follicle cells from D.yakuba and D.ananassae was critical. The Lau lab achieved this using a methodology they developed for profiling Piwi-interacting RNAs from these cells (Matts, Synikova et al. 2013).

Figure 6: Evolution of enhancer activity in OSCs and gene expression in follicle cells in vivo.

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Arnold CD, Gerlach D, Spies D, Matts JA, Sytnikova YA, Pagani M, Lau NC, Stark A. Nat Genet. 2014 Jun 8. doi: 10.1038/ng.3009. [Epub ahead of print] Quantitative genome-wide enhancer activity maps for five Drosophila species show functional enhancer conservation and turnover during cis-regulatory evolution.

Matts JA, Sytnikova Y, Chirn GW, Igloi GL, Lau NC. Methods Mol Biol. 2014;1093:123-36. doi: 10.1007/978-1-62703-694-8_10. Small RNA library construction from minute biological samples.

 

Now available: genome stability

genomestablilityProfessor of Biology Jim Haber‘s new book, Genome Stability: DNA Repair and Recombination, five years in the making, has appeared in print this month. The table of contents and a sample chapter can be checked out on the publisher’s website. As always, check Jim’s website (or PubMed) to see new research from the lab. New this month in Nature Structural & Molcular Biology: Dynamics of yeast histone H2A and H2B phosphorylation in response to a double-strand break.

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Eapen wins HHMI International Student Research Fellowship

Vinay Eapen from the Haber Lab in Biology has been awarded an HHMI International Student Research Fellowship. These fellowships, highly sought-after, are among the few available to international students studying at major research universities in the US – there were only 42 recipients nationwide. Eapen is a graduate student entering his fourth year in the Molecular and Cell Biology PhD program at Brandeis, and already has 4 publications from Brandeis to his credit resulting from his studies of the DNA damage checkpoint and autophagy in yeast.

 

How yeast switch mating type and why we care

For grad students needing background on work in the Haber lab studying DNA recombination and repair, there are a couple new papers out to help you. A new review by Prof. Haber entitled Mating-type genes and MAT switching in Saccharomyces cerevisiae in Genetics provides a detailed introduction to literature. There’s a lot there… as Jim says in the Acknowledgements

The part of this work that derives from my own lab has been carried out for more than 30 years by an exceptional contingent of graduate students, postdoctoral fellows, technicians, and Brandeis University undergraduates […]

If methods papers are what you need instead, check out Sugawara & Haber (2012), Monitoring DNA Recombination Initiated by HO Endonuclease in Methods in Molecular Biology.

Sept 18 Symposium on Stem Cell Genetics

On September 18th, 2012, the Molecular and Cell Biology graduate students supported by our  Genetics Training Grant from NIGMS will be hosting a symposium entitled “Stem Cell Genetics: Insights and Applications”. We will be joined by four distinguished scientists who will be presenting their recent work:

Rudolf Jaenisch (Whitehead Institute), our Keynote Speaker, will speak to us about the epigenetic regulation of gene expression in development and cell differentiation;
Constance Cepko (Harvard Medical School) will present her work on the development and degeneration of the vertebrate central nervous system, using the retina as a model;
Fernando Camargo (Harvard Stem Cell Institute) will talk about the molecular basis of tissue size regulation and the role of transcription factors and micro RNAs in hematopoietic stem cell fate;
Konrad Hochedlinger (MGH) will present work on mechanisms underlying pluripotency in embryonic stem cells and nuclear reprogramming.

The talks will take place in the Shapiro Campus Center Theater, and we also invite you to join us at the subsequent Poster Session and Reception. Current and former trainees supported by the Genetics Training Grant will be presenting posters from 3:40 to 5:00 PM on the 2nd floor of the Shapiro Science Center. In addition, all life sciences graduate students are encouraged to present posters.

The entire event is free and open to the public. For planning purposes, we ask anyone attending the symposium and/or presenting a poster to pre-register at http://www.bio.brandeis.edu/gtg_symposium/ by September 10th, 2012. You can also visit this website to see the symposium schedule, and to see the list of poster titles after registration is complete.

Please join us for this exciting symposium showcasing genetics at Brandeis!

Blanca Carbajal-Gonzalez
Marissa Donovan
Adam Johnston
Cara Pina
Andy Russell
Mike Spellberg

Genetics Training Grant Symposium to be held Sep 2

The Genetics Training Grant at Brandeis (GTG) is an important part of the graduate programs in Molecular & Cell Biology and Biochemistry & Biophysics, teaching students to critically evaluate both their own research and the scientific literature, while also developing their communication skills. The annual symposium, organized and hosted by the GTG students, is central to this mission. This year’s GTG Symposium is entitled “Signal Transduction: Insights gained from diverse species”, and will take place on September 2.  Four distinguished scientists will be presenting their recent work:

  • Gary Ruvkun (Harvard Medical School), our Keynote Speaker, will speak about neuroendocrine control of C. elegans development, metabolism and longevity;
  • Marcia Haigis (Harvard Medical School) will present her work on mitochondrial sirtuins and aging;
  • Morris White (Children’s Hospital Boston) will talk about the molecular basis of mammalian insulin-like signaling in the pathophysiology of metabolic disease;
  • Cynthia Bradham (Boston University) will present work on secondary axis specification and patterning in the sea urchin.

These talks will be followed by a Poster Session and Reception (see schedule). Current and former GTG trainees will be presenting posters from 3:40 to 5:00 PM in the Shapiro Science Center Atrium, All life sciences graduate students are encouraged to present posters.

The entire event is free and open to the public.  For planning purposes, we ask anyone attending the symposium and/or presenting a poster to pre-register by August 24th, 2011. Poster titles will be available after registration is complete.

Please join us for this exciting symposium showcasing genetics at Brandeis.

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