During division, the scientists found, MLL abandoned some of the genes that it was previously shackled to. Instead, for the duration of mitosis, MLL shifted to a new set of genes. This set, the team discovered, constitutes all the genes that were the most highly active before division triggered a blackout of all gene activity.

Such genes face the challenge of quickly reactivating to their previous high levels after division ends. "By seeking out and bookmarking this cohort of highly-expressed genes during division, MLL delivers a post-mitotic kick that helps turn genes back on," explains Vakoc. In support of this idea, his team found that when MLL was depleted, the reactivation of these genes was delayed and they "kicked" on more slowly. By staying tethered to these genes, MLL provides a beacon to which other proteins can home to, thereby jump-starting gene activity.

Vakoc is now exploring how the mutations that increase the activity of MLL in leukemia affects the gene reactivation pattern in new cells and how this might contribute to the abnormal cell proliferation and differentiation seen in leukemia.

Source: Cold Spring Harbor Laboratory