Embryonic stem cells go through large amounts of changes during differentiation into specific cell types. The changes must extend to, if not origin from reorganization of the genomes of these cells, which would most likely involve genetic and epigenetic (not encoded for in DNA sequence) factors. Epigenetic modification systems control stability of gene expression during cell/organism development or possibly also during diseased states. One of these epigenetic regulators is the post-translational modification of chromatin- associated proteins such as histones and high-mobility group (HMG) proteins. These modifications have been shown to modulate a variety of biological events such as gene activation, gene silencing or have roles in DNA repair mechanisms. Using high end mass spectrometry, an in-depth investigation of the modification states of histones and HMG proteins from stem and differentiated cells will be performed in both a qualitative and quantitative manner. This research proposal provides a solid start in understanding the epigenetic mechanisms that may be involved in cellular differentiation and could yield significant information that could lead to improved stem cell technology for therapeutic applications. ? ? ?
| Garcia, Benjamin A; Thomas, C Eric; Kelleher, Neil L et al. (2008) Tissue-specific expression and post-translational modification of histone H3 variants. J Proteome Res 7:4225-36 |
| Garcia, Benjamin A; Shabanowitz, Jeffrey; Hunt, Donald F (2007) Characterization of histones and their post-translational modifications by mass spectrometry. Curr Opin Chem Biol 11:66-73 |
| Garcia, Benjamin A; Pesavento, James J; Mizzen, Craig A et al. (2007) Pervasive combinatorial modification of histone H3 in human cells. Nat Methods 4:487-9 |
