Open AccessA human histone H4 gene exhibits cell cycle-dependent changes in chromatin structure that correlate with its expression.
Author(s) -
Susan A. Chrysogelos,
Donald E. Riley,
Gary S. Stein,
Janet L. Stein
Publication year - 1985
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.82.22.7535
Subject(s) - chromatin , biology , microbiology and biotechnology , dnase i hypersensitive site , histone , histone h4 , micrococcal nuclease , nuclease , histone h2a , cell cycle , dna replication , gene , deoxyribonuclease i , gene expression , nucleosome , genetics , promoter , base sequence
By use of synchronized human HeLa S3 cells, a site sensitive to both DNase I and nuclease S1 was identified 50-150 base pairs upstream of the ATG codon of a cell cycle-dependent histone H4 gene. This site expanded to include a broad region of approximately equal to 300 base pairs sensitive to DNase I throughout S phase and then narrowed again to the original site after the completion of DNA replication. The level of nuclease S1 sensitivity was greatest during early S phase, when the gene is replicated and its transcription rate is maximal. The chromatin structure of the human beta-globin gene, which is not expressed in HeLa cells, was also analyzed throughout the cell cycle, and in no case was a sub-band seen as a result of DNase I or nuclease S1 digestion, nor were there any changes in nuclease sensitivity correlated with its replication. Thus the cell cycle-dependent chromatin alterations in this histone H4 gene appear to be due to the coupled replication and expression of this gene rather than simply its replication. These results suggest that histone genes, as compared with developmentally regulated genes, exhibit an "intermediate" level of regulation whereby the gene is never in a completely inactive conformation, but changes in chromatin structure occur as a function of the cell cycle and expression.