We have identified a number of nonallelic histone variants which are involved both in the replication of chromosomes and in the maintenance and repair of tissue-specific patterns of chromatin conformation, an important mechanism for preserving the normal patterns of gene expression in long-lived, nondividing cells of adult mammals. We have identified several distinct modes of expression of histone gene clusters in the mouse genome using several histone variant mutants discovered by us. We have found the expression of different histone variants changes at the time of commitment of cells to terminal differentiation and that histone variant ratios are useful indicators of spontaneous or induced rates of cell turnover or regeneration in adult tissues. We are using histone variant ratios as an assay for studying commitment to terminal differentiation, a likely common defect in cancer cells, as well as for the development of a safe clinical test for chronically increased rates of cell turnover which may be an important cause of premature aging and tumor promotion. (D)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA015135-12
Application #
3164096
Study Section
Physiological Chemistry Study Section (PC)
Project Start
1977-04-01
Project End
1987-03-31
Budget Start
1985-04-01
Budget End
1987-03-31
Support Year
12
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Fox Chase Cancer Center
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19111
Zweidler, A (1992) Role of individual histone tyrosines in the formation of the nucleosome complex. Biochemistry 31:9205-11
Morris, R L; Keller, L R; Zweidler, A et al. (1990) Analysis of Chlamydomonas reinhardtii histones and chromatin. J Protozool 37:117-23
Rizzo, P J; Morris, R L; Zweidler, A (1988) The histones of the endosymbiont alga of Peridinium balticum (Dinophyceae). Biosystems 21:231-8