Role of Transcription Factors GATA1 and MLL in Mitotic Bookmarking in Normal and Leukemic Cells
Tissue-specific transcription patterns are preserved throughout cell divisions (mitosis) to maintain lineage fidelity and normal cell development. During mitosis, gene transcription is silenced and most transcription factors are removed from chromatin.
The molecular mechanisms that allow transcription to resume in an orderly fashion in newborn cells following mitosis is commonly called “mitotic book marking” or mitotic memory. Because uncontrolled cell division is a hallmark of malignant cell growth, understanding the molecular basis of mitotic book marking may provide greater insights into basic mechanisms of cancer maintenance.
By studying the mixed lineage leukemia (MLL) protein and the hematopoietic transcription factor GATA1, Gerd A. Blobel, MD, PhD, and researchers at the Center for Childhood Cancer Research have gained greater insights of the underlying molecular mechanisms of mitotic bookmarking. This includes a functional role for GATA1 in the post-mitotic reactivation of bookmarked genes.
Experiments are underway to determine how GATA1 is retained at some chromatin binding sites but not others during mitosis. Other studies are directed at determining whether mitotic retention of MLL translocation fusion proteins, characteristic of many infant leukemias, is different from that of normal MLL and whether mitotic memory is perturbed in MLL-rearranged leukemic cells.
Ultimately, a better understanding of factors that participate in mitotic memory may lead to identification of new therapies to treat hematologic cancer and related blood disorders.