Reverse Transformation and Genome Exposure in the C6 Glial Tumor Cell Line

Reexpression of growth control and differentiation in response to physiological inducers can be demonstrated in some malignant cell lines, showing that they are not irreversibly transformed. This switch in phenotype is likely to reflect a changing pattern of gene expression, but it has not been known whether such cellular transitions involve major or only minor modulation of chromatin structure. We have studied growth control and accessibility of chromatin to DNase I in C6 glioma cells subjected to different growth regimens using an in situ nick translation assay to label the most exposed regions of nuclear chromatin. In fibroblasts and primary glia, exposed chromatin was localized mainly at the nuclear lamina. This readily labeled DNA structure was largely lacking in the malignant C6 glioma. When C6 cells were treated with dibutyryl cyclic AMP, exposed chromatin was reestablished around the nuclear periphery. This restoration of a normal genome exposure pattern required cytoskeletal integrity. Thus large...