CHARLOTTESVILLE, Va., June 4, 2007 A team of researchers led by University of Virginia Health System geneticists has uncovered a major secret in the mystery of how the DNA helix replicates itself time after time. It turns out that it is not just the sequence of the bases (building blocks) in the DNA, but also how loosely or tightly the chromatin (the material that makes up chromosomes) is packed at different points of the chromosome that is critical.
Where chromatin is packed more loosely, the genes are replicated earlier than other genes and are expressed at high levels. Where chromatin is dense, these genes are replicated later and are not expressed.
Our work showed that by looking at time of replication, we could predict which genes are in an environment that could be expressed and the potential that cell has of going down different paths of differentiation, says Anindya Dutta, M.D., UVa professor of biochemistry and molecular genetics, who headed the replication portion of the major ENCODE project published in Nature journal (June 14). The time of replication of different parts of our genome is very nicely correlated with the chromatin packaging.
This finding held true for both cell lines studied, the HeLa cervical cancer cell line and a normal cell line (lymphocytic cells). To our surprise, what the HeLa cells were predicting in terms of chromatin packaging held true in the lymphocytes, even though the HeLa cells are cancer cells with scrambled genes, Dutta said. The chromatin packaging predictions were approximately comparable.
Chromosomes, then, are not just a framework of DNA but also are influenced by the proteins that pack the DNA, particularly histones. This packaging determines how the cells enzymes get access to the DNA to read off the DNA and replicate, ultimately to create all of the proteins needed by a given cell.