| 研究実績の概要 |
Rationale and design:
Loss of telomere maintenance and transposon derepression are known to be causal factors for tumor development. The drosophila telomeres are unique in animal kingdom as they are made up of transposons. The telomere maintenance in Drosophila germline and in human embryonic stem cells share many regulatory core components such as heterochromatin Protein, HP1 and a histone methyl transferase, SetDB. We investigated HP1a role in the Drosophila germline in maintaining stem cells and fertility.
Work done and Results:
We found that HP1a loss results in female sterility and defects in the germline stem cell maintenance and division. The HP1a loss leads to derepression of telomeric transposons and telomere elongation. Our results show that HP1a suppresses the telomeric transposons in piRNA dependent manner, by stabilizing the telomeic piRNAs in nucleus bound to Piwi protein. We then analyzed RNA expressing profile in HP1 knockdown and Piwi-bound small RNAs in the gonads lacking HP1a function in the germline cells. These experiments gave us a clear idea that HP1a absence in germline predominantly causes loss of piRNAs arising form the telomeric regions. Biochemical and genetic experiments, done in the grant period, showed that HP1a is not required for the transcription of precursors or their transport to the site of processing. Rather, HP1a absence in germline leads to loss of Piwi-bound telomeric piRNAs, strongly suggesting that HP1a specifically stabilizes the telomeric piRNAs (Manuscript in preparation)
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