Histone-modifying enzymes moonlight in mitosis to regulate chromosome congression
we have previously reported a transcription- and methylation-independent role of MLL complex during mitosis. Work from our laboratory reveals that MLL complex localizes to spindle microtubules, and RNAi of the MLL complex severely compromises chromosome alignment during metaphase. Our studies uncover interactions of the MLL complex with kinesin and dynein motor proteins. We characterized the role of the MLL complex in regulating spindle localization of kinesin-13 motor protein, Kif2A. Collectively, our results show how the MLL complex functions in pathways, other than transcription, to ensure proper division of genetic material, and even loss of function of MLL in this process may be conducive to tumorigenesis. Now we are in the process of understanding other functions of MLL in regulation of mitosis and how they can provide insights into MLL-rearranged leukemia.
Figure 2. Loss of MLL results in chromosome misalignment.MLL localizes to the spindle microtubules in mitosis. In control siRNA treated cells, MLL is present on the spindle, and chromosomes are aligned properly (metaphase cells are shown). Upon loss of MLL, the spindle is distorted and as a result chromosomes are unable to align, resulting in errors in segregation.
