RNA interference (RNAi)-related mechanisms participate in diverse epigenetic phenomena. Few are more extreme than the genome remodeling of the ciliate Tetrahymena thermophila. This organism eliminates nearly 15 megabases of its germline DNA from the somatic nucleus during its development. Our lab aims to understand the regulation of this massive genome reorganization using a combination of genetic, molecular, and cellular biology approaches to uncover how ~6000 DNA segments are selectively excised. Our current model is built on the observations that bi-directional germline transcription leads to the generation of 28-30 base RNA molecules (scan RNAs) that then target specific chromatin modification(s) to the homologous locus. The DNA rearrangement machinery recognizes the modified chromatin state and eliminates the targeted DNA segment. These studies will certainly provide fundamental insight into RNAi-related mechanisms that direct chromatin modifications that are critical for transcriptional gene silencing and heterochromatin formation in eukaryotes. Underlying this proposal is a goal to understand how RNA molecules can communicate genetic information between the parental and developing genomes, which has great potential to reveal novel roles for RNA in epigenetic programming. Additionally, we believe many of the DNA segments targeted for elimination are important for germline chromosome structure, and thus understanding how the cell specifically recognizes these sequences will contribute general knowledge of mechanisms ensuring chromosome stability that are essential to prevent aberrant rearrangements.

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Nuclear development occurs during Tetrahymena mating. Shown here is a conjugating pair shortly before the genome reorganization initiates. The DNA deletion protein, Pdd1p, fused to green fluorescent protein, is localized on the chromatin of the large, developing somatic nuclei.