The working hypothesis is that the genetic material of the cell has a varigated pattern of domains differing in degree of condensation (aggregation) such that active genes lie in uncondensed domains and inactive ones in aggregated domains. H1 histones are expected to maintain this varigated pattern and to aid in the propagation of the patterns through cell division. It is proposed to fractionate chromatin into four fractions (H1-free; soluble aggregation resistant; soluble aggregation prone-and nuclear matrix attached domains) and analyse their compositional differences (variants of H1 and other histones, histone and DNA modifications, kinds of DNA non histone chromosomal proteins). The interactions of H1 variants, HMG 1 and 2, and DNA's of various physical conformations will be studied to see how modulation (short term) of the varigated pattern might be achieved. Metabolic turnover of H1 variants, and the timing of synthesis of different variants within S phase of the cell cycle, will be correlated with the power of the variants to condense DNA, and their degree of enrichment in aggregation prove chromatin. This will test the hypothesis that the capacity of H1 to condense DNA and chromatin is used in vivo to maintain a self propagating pattern of chromatin condensation through the cycle. Learning if and how H1 histones and HMG 1 and 2 maintain the commitment of a cell to a particular pattern of gene expression in terms of structural condensation of the chromatin is related to all health problems that involve aberrations in growth and phenotype, (e.g. cancer, mutagenesis, genetic disorders).
