Meiosis represents a highly ordered series of events that results in the production of haploid gametes; it plays a central role in the reproduction of essentially all diploid organisms. As an experimental system, meiosis provides a valuable system to study many aspects of cellular function, including changes in chromatin conformation, recombination, nuclear and cellular division, and cell cycle control mechanisms. Through the analysis of the y9287 knockout mutation of Arabidopsis, which is defective in meiotic cell cycle control, a PHD domain containing protein has been identified. The phenotype of the y9287 mutation and the presence of nuclear-localization signals and the PHD domain suggest that Y9287 may participate in controlling meiotic gene expression or chromatin remodeling during meiosis. Experiments outlined in this proposal are designed to investigate these possibilities by determining the expression and localization patterns of Y9287 and by isolating proteins that interact with Y9287. In addition, preliminary experiments to isolate and characterize mutations in three additional Y9287-like PHD domain containing proteins are described to investigate their functions and determine it one or more are required for other aspects of meiosis. Information obtained from the studies outlined here will contribute significantly to our understanding of a number of areas, including (1) regulation of the meiotic cell cycle, (2) PHD-domain containing proteins and their role(s) in meiosis and (3) cell cycle control processes in general. Results from these experiments should also have significant health relevance. The process of meiosis lies at the heart of human reproduction. Given the numerous common themes observed between meiosis in different species, information obtained from this work should provide valuable insight into vertebrate systems. Furthermore, understanding the cell cycle and its control is critical to numerous different aspects of human health. Proper control of the cell cycle is responsible for cell growth and differentiation. Alterations in the cell cycle, specifically loss of control, are responsible for countless diseases. Finally, PHD-domain containing proteins have been associated with several diseases, including, Williams syndrome, head and neck squamous cell carcinomas, myeloid leukemia and autoimmune polyglandular syndrome type 1. Therefore, our studies will provide significant new insights into events associated with the meiotic cell cycle and the role(s) of PHD domain proteins, which should be applicable to numerous different systems.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
2R15GM055956-02A1
Application #
6508081
Study Section
Genetics Study Section (GEN)
Program Officer
Zatz, Marion M
Project Start
1997-06-01
Project End
2005-06-30
Budget Start
2002-07-01
Budget End
2005-06-30
Support Year
2
Fiscal Year
2002
Total Cost
$140,000
Indirect Cost
Name
Miami University Oxford
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
041065129
City
Oxford
State
OH
Country
United States
Zip Code
45056
Yang, Xiaohui; Makaroff, Christopher A; Ma, Hong (2003) The Arabidopsis MALE MEIOCYTE DEATH1 gene encodes a PHD-finger protein that is required for male meiosis. Plant Cell 15:1281-95
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