The objectives of this research are to determine the molecular effects of histone acetylation and phosphorylation and to elicit their roles in transcriptions, cell proliferation, and chromosomal condensation. This program has evolved along two lines (1) definition of histone modifications by determination of extent of modification and the occurrence of modification during the cell cycle or in response to chemical agents; and (2) utilization of information gained in the first approach to determine the molecular effects of histone modifications. Histones are isolated from synchronized cell cultures or chemically-treated cultures to maximize a given histone modification. The effects of histone modification upon histone conformation, histone-histone interactions, histone DNA interactions, and chromatin structure are being investigated. These investigations employ cell synchrony methods, radiolabeling, circular dichroism, ultracentrifugation, DNA nuclease digestion, and various systems of electrophoresis.