Recipes for Regulation of the Genome: Charge, Grease and Intrinsic Disorder
We are interested in understanding how post-translational modifications and protein intrinsic disorder regulate genome usage, transcriptome regulation, and RNA processing. This has been broadly referred to as epigenetics.
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 address these questions, including: protein biochemistry and enzymology, structural biology, mass spectrometry, 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 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 how PRMTs regulate transcription and RNA splicing - we use genomics, sequencing, bioinformatics, and other quantitative approaches
- Determining how TTLL4-mediated post-translational glutamylation of histone chaperones (including Npm1, Npm2, and Nap1) occur, how glutamylation regulate histone chaperones - in normal conditions and in cancers like AML
- Using quantitative techniques (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.