POSTTRANSLATIONAL MODIFICATIONS ON HISTONES AND HISTONE VARIANTS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Multicellular organisms consist of various cell types with the same genetic information but a high degree of differentiation, characterized by a unique pattern of gene expression for each cell type. Establishment and maintenance of these diverse expression patterns is fundamentally important for cell identity and organism survival, and aberrant gene expression in a single cell can lead to developmental abnormalities or cancer. Epigenetic regulatory mechanisms employ dynamic modifications in chromatin structure, such as histone methylation, acetylation, phosphorylation and ubiquitination, to regulate gene expression. These posttranslational modifications are integrated in a combinatorial fashion to provide cells with transcriptional memory to stably maintain gene expression patterns throughout many divisions, and developmental flexibility to facilitate programmed alterations in gene expression. Equipped with the unprecedented sensitivity and structural specificity offered by tandem mass spectrometry, we are hoping to elucidate the nature and functional role of the rich epigenetic information in mammalian chromatin.