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Chromatin structure remodeling complexes control germ cell fate in C. briggsae

by
Xiangmei Chen
B.S., 2004
Yunnan University, China

Thesis Advisor: Ronald Ellis, Ph.D.

Cell and Molecular Biology Program

Science Center, Room 290

Thursday, April 25, 2013
12 pm


Abstract

Changes in cis-regulatory sequences have been the center of molecular evolutionary research. These changes can alter gene expression temporally or spatially, creating variations in phenotype that are subject to natural selection. However, little is known about the roles that chromatin regulators or nuclear transport machinery might play in this process. In Caenorhabditis, the fog-3 gene plays a conserved role in the decision of germ cells to undergo spermatogenesis. Moreover, all fog-3 promoters contain binding sites for the transcription factor TRA-1, and fog-3 transcripts are only found in animals producing sperm. Here, we show that fog-3 activity in C. briggsae is regulated by two different chromatin remodeling complexes, the Tip60 Histone Acetyl Transferase complex, and the Nucleosome Remodeling Factor (NURF) complex. We also show that a key component of the nuclear transport machinery, IMB-2, is required for spermatogenesis. First, TRR-1 and other members of the Tip60 complex act through TRA-1 to increase the level of fog-3 transcripts and control some somatic fates. These functions of Tip60 are conserved among nematodes. Because Tip60 is required for spermatogenesis, it is likely to work by helping TRA-1 activate target genes. Second, the NURF complex is essential for spermatogenesis, viability, and germ cell proliferation. Moreover, it works by promoting the transcription of fog-1 and fog-3 independent of TRA-1, which places its activity at the end of the sex-determination pathway. Surprisingly, this role of the NURF complex has changed during recent nematode evolution. Finally, we show that a homolog of the human importin-B, IMB-2, also regulates the sperm/oocyte decision.


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