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TCNP News

Seminars & Miscellaneous
Hot Papers
**New Feature**:  Upcoming Scientific Conferences of Interest
IcePick In Action
PTM Humor


Seminars & Miscellaneous

As of January 1, 2009, please refer to the TCNP Google Calendar for a more comprehensive list of TCNP seminars of interest.

**October 5, 2009** - This TCNP heartily congratulates our colleague, Dr. CAROL GREIDER, PhD, on being awarded the 2009 Nobel Prize in Physiology or Medicine by the Royal Swedish Academy of Sciences.  She shares the award with Drs. Elizabeth Blackburn (UCSF) and Jack Szostak (Harvard Medical School) for their pioneering work on the mechanism and regulation of telomere maintenance.   Hopkins Press Release

Interview with Akhilesh Pandey on "Discoveries, Databases & the Sociology of Science"

Photos from the May 19, 2009 Special IBBS/NIH Roadmap Minisymposium

BCMB Thesis Seminar

Tuesday, December 16, 2:00 pm, 517 PCTB
"Silencing an old dog and some new tricks:  Function of the nucleosome LRS domain"
Anne Norris, PhD Candidate in The Boeke Lab

BCMB Thesis Seminar

Tuesday, November 11, 3:00 pm, 517 PCTB
"Functional Dissection of the Essential Nucleosome Acetyltransferase of H4 (NuA4) Complex with Genomics and Proteomics Approaches"
Yu-yi Lin, PhD Candidate in The Boeke Lab


See our IcePick frozen strain & plasmid distribution system prototype in action!


HOT PAPERS from our TCNP of Lysine Modification

  • Lin Y-Y, Lu J-Y, Zhang J, Walter W, Dang W, Wan J, Tao S-C, Qian J, Zhao Y, Boeke JD, Berger SL, Zhu H. (2009). Protein acetylation microarray reveals NuA4 controls key metabolic target regulating gluconeogenesis. Cell. 136, 1073-1084.  PubMed Link

    A proteome-wide search for nonhistone substrates of the essential nucleosome acetyltransferase of H4 (NuA4) complex was carried out using yeast proteome microarrays.  Among newly identified substrates are many cytoplasmic metabolic enzymes known to respond to extracellular nutrient sources and/or intracellular energy status.  Acetylation of phosphoenolpyruvate carboxykinase (Pck1), the rate-limiting enzyme in gluconeogenesis, turns out to be crucial for its enzymatic activity both in yeast and in human hepatocellular carcinoma (HepG2) cells.  This indicates an unexpected extra-nuclear function of NuA4 in regulating metabolism in addition to its well-known roles in regulating chromatin-related processes, and suggests that the two processes are somehow coupled.  Furthermore, deacetylation of Pck1 by the histone deacetylase Sir2 suggests reveals a connection between gluconeogenesis and chronological life span in yeast.
     
  • Dai J, Hyland EM, Yuan DS, Huang H, Bader JS, Boeke JD. (2008). Probing nucleosome function: A highly versatile library of synthetic histone H3 and H4 mutants. Cell. 134, 1066-1078.  PubMed Link

    To probe nucleosome function in vivo, Dai and Hyland constructed a yeast library of 486 histone H3 and H4 mutants. The library includes both systematic substitutions and tail deletion alleles, and the design features enable analysis of each mutant either episomally or at the endogenous locus. Moreover, each mutant is tagged with unique molecular barcodes to facilitate phenotypic analysis of complex pools of histone mutants using repurposed microarrays previously designed for analyzing yeast knockout collections. Such phenotypic analysis mapped nucleosome surfaces required for transcriptional silencing, response to genome stress, fitness in a chemostat, and NHEJ. This collection of histone mutants will enable researchers to probe nucleosomal function in response to myriads of growth conditions or genetic alterations and should elucidate cis- and trans-acting signals for lysine modification within the nucleosome. Construction of more H3 and H4 mutants, as well as histone H2A and H2B mutants are underway! A database that documents these mutations and their associated phenotypes can be found here. This mutant collection will soon be available through Open Biosystems!
       
  • Guha U, Chaerkady R, Marimuthu A, Patterson AS, Kashyap MK, Harsha HC, Sato M, Bader JS, Lash AE, Minna JD, Pandey A, Varmus HE. (2008). Comparisons of tyrosine phosphorylated proteins in cells expressing lung cancer-specific alleles of EGFR and KRAS. Proc Natl Acad Sci U S A. 105, 14112-14117.  PubMed Link
     
    Quantitative mass spectrometry in combination with SILAC was used to compare the pattern and extent of tyrosine phosphorylation in isogenic cell lines expressing either normal or cancer-specific signaling molecules.
       
  • Molina H, Yang Y, Ruch T, Kim JW, Mortensen P, Otto T, Nalli A, Tang QQ, Lane MD, Chaerkady R, Pandey A. (2008). Temporal Profiling of the Adipocyte Proteome during Differentiation Using a Five-Plex SILAC Based Strategy. J Proteome Res. [Epub ahead of print].  PubMed Link
      
  • Qi Y, Suhail Y, Lin Y-Y, Boeke JD, Bader JS. (2008). Finding friends and enemies in an enemies-only network: A graph diffusion kernel for predicting novel genetic interactions and co-complex membership from yeast genetic interactions. Genome Res. [Epub ahead of print].  PubMed Link
      
  • Evans-Nguyen KM, Tao SC, Zhu H, Cotter RJ. (2008). Protein arrays on patterned porous gold substrates interrogated with mass spectrometry: detection of peptides in plasma. Anal Chem.  80(5), 1448-1458.  PubMed Link
       
  • Ben-Aroya S, Coombes C, Kwok T, O'Donnell KA, Boeke JD, Hieter P. (2008). Toward a comprehensive temperature-sensitive mutant repository of the essential genes of Saccharomyces cerevisiae. Mol Cell. 30(2), 248-258.  PubMed Link
      
  • Lin Y-Y, Qi Y, Lu J-Y, Pan X, Yuan DS, Zhao Y, Bader JS, Boeke JD. (2008). A comprehensive synthetic genetic interaction network governing yeast histone acetylation and deacetylation. Genes Dev. 22(15), 2062-74.  PubMed Link
      
  • Chen CS, Korobkova E, Chen H, Zhu J, Jian X, Tao SC, He C, Zhu H. (2008). A proteome chip approach reveals new DNA damage recognition activities in Escherichia coli. Nat Methods. 5(1), 69-74.  PubMed Link
      
  • Lu J-Y, Lin Y-Y, Tao S-C, Zhu J, Pickart CM, Qian J, Zhu H. (2008). Functional dissection of a HECT ubiquitin E3 ligase. Mol Cell Proteomics. 7, 35-45.  PubMed Link
     
    The authors used a combination of yeast proteome chip assays, genetic screening, and in vitro/in vivo biochemical analyses to identify and characterize eight novel in vivo substrates of the yeast ubiquitylating enzyme Rsp5, a homolog of the human ubiquitin-ligating enzyme Nedd4. This work illustrates how proteome chips can be used to define probable in vivo substrates of lysine modifying enzymes.
      
  • Yang M, Culhane JC, Szewczuk LM, Gocke CB, Brautigam CA, Tomchick DR, Machius M, Cole PA, Yu H. (2007). Structural basis of histone demethylation by LSD1 revealed by suicide inactivation. Nat Struct Mol Biol. 14, 535-539.  PubMed Link
      
  • Paliwal S, Iglesias PA, Campbell K, Hilioti Z, Groisman A, Levchenko A. (2007). MAPK-mediated bimodal gene expression and adaptive gradient sensing in yeast. Nature. 446, 46-51.  PubMed Link
     
  • Pan X, Ye P, Yuan DS, Wang X, Bader JS, Boeke JD. (2006). A DNA integrity network in the yeast Saccharomyces cerevisiae. Cell. 124, 1069-1081.  PubMed Link
     
    Global patterns of synthetic lethal genetic interactions defined 16 functional modules within the genetic network governing DNA integrity in budding yeast. Modules or genes involved in DNA replication, DNA replication checkpoint signaling, and oxidative stress response were shown to be the major guardians against intrinsic DNA damage. In addition, new regulators of mitotic DNA replication and genomic stability were identified. This work provided rich data for further study of genome integrity and validated the development and use of genetic approaches to study the networks, pathways and dynamics of lysine modification.

HOT PAPERS from the Other TCNPs

Alber F, Dokudovskaya S, Veenhoff LM, Zhang W, Kipper J, Devos D, Suprapto A, Karni-Schmidt O, Williams R, Chait BT, Rout MP, Sali A. (2007). Determining the architectures of macromolecular assemblies. Nature. 450, 683-694.  PubMed Link

Alber F, Dokudovskaya S, Veenhoff LM, Zhang W, Kipper J, Devos D, Suprapto A, Karni-Schmidt O, Williams R, Chait BT, Sali A, Rout MP. (2007). The molecular architecture of the nuclear pore complex. Nature. 450, 695-701.  PubMed Link

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Upcoming Scientific Conferences of "Special K" Interest

PTM Humor

"The “Hunt” for rare and exotic histone modifications continues" by Sean Taverna originally appeared in an issue of International Journal of Mass Spectrometry dedicated to Donald Hunt (Taverna SD, Allis CD, Hake SB. (2007). Int J Mass Spectrom. 259, 40–45).

The “Hunt” for rare and exotic histone modifications continues

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