Non B DNA Structure with Chemical Carcinogens

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Accumulated evidence suggests that higher-order organization of chromatin is important in gene expression. However, little is known about how genomes are folded and organized in the cell so that specific genes are properly regulated in a cell-type specific manner. Our research group identified a nuclear protein SATB1, which has a unique function as a 'genome organizer'. We found that SATB1 has a 'cage-like' protein distribution surrounding the heterochromatin, and this protein folds chromatin by tethering specialized DNA sequences. SATB1 serves as a landing platform for the assembly of chromatin remodeling/modifying complexes with the specialized DNA sequences, thereby regulating expression of a large body of genes. Thus, SATB1 sets up a functional nuclear architecture, referred to as 'the SATB1 network', since it establishes a regulatory network with the capacity to re-program gene expression. In fact, our most recent data show that the SATB1 nuclear architecture is important in cells acquiring new functions. We plan to investigate the roles of SATB1 in the progression of different types of cancer and in development of some adult progenitor cells using conditional SATB1 knockout mice. We will also study how SATB1 spatially organizes genomic loci in the nuclei and whether it contributes in the mechanisms underlying cell memory.