Recipes for Regulation of the Genome: Charge, Grease and Intrinsic Disorder
We are interested in 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 address 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
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.