Each cell inherits genes from its parent as well as epigenetic information - what amounts to an instruction manual that specifies which genes should be activated or "expressed," when and to what level. Cold Spring Harbor Laboratory (CSHL) scientist Chris Vakoc, M.D., Ph.D., and his team have now discovered how some of these epigenetic instructions get stably transferred from one generation of cells to the next.
The scientists report that newly formed cells inherit the knowledge of which genes need to become highly active right away thanks to a helpful protein that "bookmarks" these genes during the division of their parent cell. Their findings appear in the December 24th issue of Molecular Cell.
The bookmarking protein, called Mixed Lineage Leukemia or MLL, is notorious for triggering leukemia when the gene that encodes it becomes mutated. MLL mutations are among the most common genetic aberrations in leukemia, occurring in about 10% of leukemia cases.
"We now have a clearer picture of what MLL normally does in healthy cells to help gene expression information to travel from parent cells to daughter cells," said Vakoc. "These findings may help us understand how mutated MLL subverts inheritance mechanisms in leukemic cells."
During cell division or "mitosis," all gene activity is temporarily shut down. The dividing cell's chromosomes-the X-shaped coils of DNA-condense into tight clumps and expel most proteins that cling to DNA to maintain gene expression.
Vakoc's team was surprised to find, however, that unlike other chromosome-bound molecules, the MLL protein stays tethered to chromosomes during mitosis. Genome-wide surveys that compared MLL's chromosomal binding sites before and during division-the first comparison of its kind-revealed a second twist.