Bazett-Jones, David P. - University of Toronto

研究领域

Our hypothesis is that in mammalian cells the activity of a given gene is a function of its three-dimensional location and organization within its chromosome territory and with respect to other “subnuclear organelles” or sub-compartments in the nucleus. Therefore, the transcriptional program of each cell type should correlate with an ultrastructural signature of chromatin domains within the nuclei of cells of a given cell/tissue type. Promyelocytic leukemia nuclear bodies (PML NBs or NBs) are a class of subnuclear organelles that contribute to the compartmentalization of nuclear proteins. This process must be important because PML NBs play a central role in cellular differentiation and tumour suppression. Indeed, a number of human cancers are characterized by the down regulation or mutations of PML, including acute promyelocytic leukemia, prostate and colon. Though implicated in processes such as transcription, DNA damage repair, and apoptosis, the exact function of PML NBs is not known. A prevailing model is that they are storage sites of nuclear proteins, serving as platforms from which they move into the nucleoplasm to carry out their functions. By studying the structure, biochemical composition and dynamics of PML NBs, studies from my laboratory support another model. Though our model does not exclude the storage or platform concepts, we propose that PML NBs interact directly with the surrounding chromatin, and thereby perform a more active role in servicing the regulation of genes on their periphery.

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Nano-dissection and sequencing of DNA at single sub-nuclear structures Chen BK, Anchel D, Gong Z, Cotton R, Li R, Sun Y, Bazett-Jones DP. Small. 2014 Aug 27;10(16):3267-74 Read Electron spectroscopic tomography of specific chromatin domains. Even-Faitelson L, Fussner E, Li R, Strauss M, Bazett-Jones DP. Methods Mol Biol. 2013;1042:181-95 Read Open and closed domains in the mouse genome are configured as 10-nm chromatin fibres. Fussner E, Strauss M, Djuric U, Li R, Ahmed K, Hart M, Ellis J, Bazett-Jones DP. EMBO Rep. 2012 Nov 6;13(11):992-6. Read