Faculty Profile

Dr. David Shechter, Ph.D.

David Shechter, Ph.D.

Associate Professor, Department of Biochemistry

Areas of Research: Chromatin biology and epigenetics in development and cancer; structural and post-translational regulation of histone chaperones; molecular mechanisms and biological function of protein arginine methyltransferases

Professional Interests

NEW: You can obtain the TM0936 SAH Deaminase plasmid clone for our EZ-MTase asay (Burgos et al 2017) from DNASU: http://dnasu.org/DNASU/GetCloneDetail.do?cloneid=84735

Lab Chat with Dr. Shechter: http://magazine.einstein.yu.edu/winterspring-2017/lab-chat-5/ and Journal of Molecular Biology biography. 

Chromatin and the Biochemistry of Epigenetic Information

Our research interests are focused on understanding chromatin, the complex of DNA, histones, and other proteins that constitute the physiological form of the genome. In particular, we are interested in the role of histone post-translational modifications and histone chaperones in establishing an embryonic epigenetic state, how this process is misregulated in cancers, and how to drug components of the machinery.

Epigenetics is a phenomenon important for an overall increase in the complexity of the genome without changes in gene sequence. Post-translational modifications of histones, and deposition of histone variants, establish a “histone code” of activation or repression of transcription and other chromatin-mediated transactions, and constitute a major part of the epigenome. Epigenetic information is information content "on top of" the DNA-encoded genetic material. Epigenetic information is the landscape on which the dynamic usage of genetic information is encoded.

We utilize a wide range of techniques to broadly adress these questoins, including: protein biochemistry and enzymology, structural biology, cancer cell culture, and embryos of the frog Xenopus laevis . These tools allow us to probe evolutionarily conserved mechanisms specifying critical events in chromatin biology and epigenetics. Our combined use of rigorous in vitro studies along with in vivo studies in the frog and in cancer cells provides an uncompromised approach to fully understanding epigenetic phenomena and how to apply this knowledge towards improving human health. We are currently pursuing a number of specific research avenues, including:

  • determination of the biochemical mechanisms of arginine methyltransferases (PRMT1-9) using enzymology and structural biology
  • analyzing the histone and non-histone code specified by PRMT-catalyzed histone methylation in embryos and breast and lung cancer cells
  • Determining how phosphorylation, methylation, and glutamylation of histone chaperones (including Npm1, Npm2, and Nap1) occur and how these post-translational modifications regulate histone deposition activity
  • Using quantitative techniques (hydrogen-deuterium exchange, NMR, crystallography, binding studies) to understand histone chaperone intrinsically disordered domains in the binding and release of histones

Selected Publications

  1. Emmanuel S. Burgos,  
  2. Christopher Warren and David Shechter. Fly Fishing for Histones: Catch and Release by Histone Chaperone Intrinsically Disordered Regions and Acidic Stretches. J Mol Biol2017 doi:10.1016/j.jmb.2017.06.005
  3. Wei-lin Wang and David ShechterChromatin assembly and transcriptional cross-talk in Xenopus laevis oocyte and egg extracts. Int J. Dev. Biol. 2016. doi: 10.1387/ijdb.160161ds
  4. Hongshan Chen, Benjamin Lorton, Varun Gupta, and David Shechter. A TGFβ-PRMT5-MEP50 axis regulates cancer cell invasion through histone H3 and H4 arginine methylation coupled transcriptional activation and repressionOncogene, Jun 2016.
  5. Takashi Onikubo, Joshua J. Nicklay, Li Xing, Christopher Warren, Brandon Anson, Wei-Lin Wang, Emmanuel S. Burgos, Sophie E. Ruff, Jeffrey Shabanowitz, R. Holland Cheng, Donald F. Hunt, and David Shechter. Developmentally Regulated Post-Translational Modification of Nucleoplasmin Controls Histone Sequestration and Deposition. Cell Reports, Mar 11 2015; doi:10.1016/j.celrep.2015.02.038
  6. Histone H2A and H4 N-Terminal Tails are Positioned by the MEP50 WD-Repeat Protein for Efficient Methylation by the PRMT5 Arginine Methyltransferase. Emmanuel S. Burgos, Carola Wilczek, Takashi Onikubo, Jeffrey B. Bonanno, Janina Jansong, Ulf Reimer and David Shechter. Journal of Biological Chemistry, 2015.
  7. The PRMT5 arginine methyltransferase: many roles in development, cancer, and beyond. Nicole Stopa, Jocelyn Krebs, David Shechter. Cellular and Molecular Life Sciences2015. 
  8. Seeing beyond the double helixDavid Shechter., Journal of Pediatric Ophthalmology and Strabismus., 2014. 5:268.
  9. Phosphorylation and arginine methylation mark histone H2A prior to deposition during Xenopus laevis development
    Wei-Lin Wang, Lissa C Anderson, Joshua J Nicklay, Hongshan Chen, Matthew J Gamble, Jeffrey Shabanowitz, Donald F Hunt and David Shechter. Epigenetics & Chromatin, 2014 7:22
  10. Structure of the Arginine Methyltransferase PRMT5-MEP50 Reveals a Mechanism for Substrate Specificity Ho MC, Wilczek C, Bonanno JB, Xing L, Seznec J, Matsui T, Carter LG, Onikubo T, Kumar PR, Chan MK, Brenowitz M, Cheng RH, Reimer U, Almo SC, Shechter D.(2013).PLoS ONE 8(2): e57008. doi:10.1371/journal.pone.0057008.
  11. Protein Arginine Methyltransferase Prmt5-Mep50 Methylates Histones H2A and H4 and the Histone Chaperone Nucleoplasmin in Xenopus laevis Eggs. Wilczek C, Chitta R, Woo E, Shabanowitz J, Chait BT, Hunt DF, Shechter D.. J Biol Chem2011 Dec 9;286(49):42221-31.  
  12. Laura Banszynski, C. David Allis, David Shechter. Analysis of histones and chromatin in Xenopus laevis egg and ooctye extractsMethods2010. Vol 51:1.
  13. A distinct H2A.X isoform is enriched in Xenopus laevis eggs and early embryos and is phosphorylated in the absence of a checkpoint. Shechter D, Chitta RK, Xiao A, Shabanowitz J, Hunt DF, Allis CD. Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):749-54. 
  14. WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase activity. Xiao A, Li H, Shechter D, Ahn SH, Fabrizio LA, Erdjument-Bromage H, Ishibe-Murakami S, Wang B, Tempst P, Hofmann K, Patel DJ, Elledge SJ, Allis CD. Nature. 2009 Jan 1;457(7225):57-62.
  15. Analysis of histones in Xenopus laevis. I. A distinct index of enriched variants and modifications exists in each cell type and is remodeled during developmental transitions. Shechter D, Nicklay JJ, Chitta RK, Shabanowitz J, Hunt DF, Allis CD. J Biol Chem. 2009 Jan 9;284(2):1064-74.
  16. Analysis of histones in Xenopus laevis. II. mass spectrometry reveals an index of cell type-specific modifications on H3 and H4. Nicklay JJ, Shechter D, Chitta RK, Garcia BA, Shabanowitz J, Allis CD, Hunt DF. J Biol Chem. 2009 Jan 9;284(2):1075-85.
  17. Extraction, purification and analysis of histones. Shechter D, Dormann HL, Allis CD, Hake SB. Nature Protocols 2007;2(6):1445-57.
  18. ATM and ATR check in on origins: a dynamic model for origin selection and activation. Shechter D, Gautier J. Cell Cycle. 2005 Feb;4(2):235-8
  19. DNA unwinding is an Mcm complex-dependent and ATP hydrolysis-dependent process. Shechter D, Ying CY, Gautier J. J Biol Chem. 2004 Oct 29;279(44):45586-93. 
  20. Regulation of DNA replication by ATR: signaling in response to DNA intermediates. Shechter D, Costanzo V, Gautier J. DNA Repair (Amst). 2004 Aug-Sep;3(8-9):901-8. Review.
  21. MCM proteins and checkpoint kinases get together at the fork. Shechter D, Gautier J. Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):10845-6. 
  22. ATR and ATM regulate the timing of DNA replication origin firing. Shechter D, Costanzo V, Gautier J. Nature Cell Biology 2004 Jul;6(7):648-55
  23. An ATR- and Cdc7-dependent DNA damage checkpoint that inhibits initiation of DNA replication. Costanzo V, Shechter D, Lupardus PJ, Cimprich KA, Gottesman M, Gautier J. Mol Cell. 2003 Jan;11(1):203-13.
  24. The intrinsic DNA helicase activity of Methanobacterium thermoautotrophicum delta H minichromosome maintenance protein. Shechter DF, Ying CY, Gautier J. J Biol Chem. 2000 May 19;275(20):15049-59.

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More Information About Dr. David Shechter

Shechter Lab Website - Research Interests, Lab Members, Protocols, Photos, etc

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Research Information