Epigenetic Regulation and Control of Cell Fate

Paul Wade
Laboratory of Molecular Carcinogenesis ; NIEHS

The fundamental processes of development and differentiation result in the production of specialized cell types with unique patterns of gene expression. The transcriptional profile of a given cell type is impacted by multiple pathways which converge at the level of chromatin. Our laboratory is actively investigating control of cell identity by a chromatin modification enzyme, the Mi-2/NuRD complex. In cell culture models of differentiated, somatic cell types, this complex participates in the maintenance of cell type specific patterns of transcription integral to the differentiated phenotype. Perturbation of Mi-2/NuRD function leads to alterations in cell type-specific patterns of transcription, with concomitant phenotypic changes. Ectopic expression of key components of the complex also leads to changes in cell phenotype. In aggregate, these results imply that the epigenome has a critical role in both the establishment and maintenance of cell fate in somatic cells and that this process might be influenced by environmental factors.