Murine erythroleukemia cells are virus-transformed erythroid precursors approximating the CFUe stage of normal erythroid differentiation. On exposure to any of a variety of inducing chemicals, they initiate a coordinated program of gene expression and cell growth characteristic of this precursor. These projects have as their aim the elucidation of factors regulating the coordinated expression of genes on different chromosomes which control characteristics of induced erythroid cell differentiation including terminal cell division and globin gene expression. Three broad objectives are defined: (1) to study alterations in DNA and chromatin structure that accompany induced differentiation and examination of their role in regulating globin gene expression, including establishment of the transcription-competent state and initiation of transcription employing molecular biological probes of chromatin and DNA configuration. Current progress includes definition of the nuclease-sensitive domain and its relationship to chromatin proteins and the analysis of chain termination signals; (2) to study the relationship between gene replication and induced transcription including the identification, isolation, and location of globin gene-associated origins of replication and other regulatory sequences; and (3) to study the nature of the process of commitment-resistant cell variants including studies of commitment-related gene expression responsible for cell growth and cell cycle control such as the p53 protein gene and others. (M)
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