The K562 cell is being studied as a model of human globin gene expression. K562 cells express embryonic and fetal hemoglobins but not hemoglobin A, Beta-globin chains, nor Beta-globin mRNA. Understanding the pattern of globin expression in K562 cells may yield insight into globin expression and hemoglobin switching in normal cells. Previous work on the integrity of the Beta-globin gene has been extended to show that chromosomal alterations do not account for the pattern of Beta-like globin expression seen in K562 cells. In addition, in situ hybridization has been used to assign the Beta-globin gene locus to the chromosome region 11p11.2 to 12. Presently, studies are underway to correlate the observed pattern of sensitivity and hypersensitivity to DNase I digestion to possible alterations in chromosome structure in the transcriptionally active Beta-globin gene. This is being done by sedimentation analysis of chromatin fragments. Additionally, future experiments are planned to footprint non-histone proteins binding to the flanking regions of active globin genes. These proteins are putative transacting factors which may have a causal relationship to gene transcription.