This international collaboration between scientists in the U.S. and Israel investigates a key question about mitosis, the process of cell division in animal, plant, and other eukaryotic cells. During mitosis, chromosomes duplicate and have to be physically separated into two new offspring cells during division. In order to physically separate the duplicated chromosomes, the structure of the chromosomes must become condensed, which interferes with using the DNA in the chromosomes as a template to transcribe messenger RNA. Cell division thereby causes a temporary pause in most gene expression. A cell’s activities are highly dependent on gene expression; for example a lung cell and a skin cell have distinct physiological roles largely due to differences in gene expression. A major unanswered question is the genetic mechanism by which the two offspring cells restore gene expression, and thus all other activities, following mitosis. The research approach for answering this question involves a combination of laboratory experiments and computational analysis. The project will teach the public about the power of interdisciplinary research through producing professional videos in collaboration with the University of California, San Diego-TV. To broaden the participation of all groups in science, the US-based lab will also partner with UCSD’s STARS (Summer Training Academy for Research Success) program.
Mitosis, a tightly regulated cell cycle phase, is critical for ensuring that cellular identity is correctly relayed to offspring cells. It involves key changes including a decrease in transcription. Initial studies showed that mitosis includes global deacetylation of histones, and that there is a mitosis-specific deacetylation of the nucleosome entering the nucleosome-depleted region of most transcribed genes. Otherwise, little is known about the roles that mitotic-specific patterns of histone marks play in regulating the transcriptional changes during and following mitosis. This project focuses on the involvement of mitotic histone deacetylations. In particular, this work focuses on three candidate histone deacetylase enzymes that are already implicated in mitosis. Pharmaceuticals will be used to inhibit selectively each of the candidate enzymes and the PIs will use genome-scale strategies to measure changes in the location and amounts of histone acetylation during the cell cycle. The PIs will also examine the extent to which the three candidates enzymes individually affect gene expression during and immediately following mitosis. Lastly, the project will establish a system to locally modify the acetylation of target loci at a specific time during the cell cycle. Such a technique would allow future studies of detailed locus-specific mitotic gene expression and reactivation kinetics. Together, the integrative approaches will enable this collaborative project to address key questions regarding the cellular means required for the proper execution of mitosis and re-establishing cellular identity after division.
This collaborative US/Israel project is supported by the US National Science Foundation and the Israeli Binational Science Foundation.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
