About the Project
The centromere is a unique chromatin domain important for proper segregation of chromosomes during mitosis. In most organisms, the position of the centromere is determined epigenetically by the centromere-specific incorporation of the H3-variant CENP-A Transcription at centromeres has been linked to the deposition of new CENP-A, although it is unclear whether transcription or the produced RNA are equally important. We and others have recently found that several components of the transcriptional machinery including RNA Polymerase II (RNAPII) and centromere-associated RNA transcripts temporally coincides with CENP-A loading in mitosis to G1. While we have evidence cells that the transcriptional process itself is required for CENP-A deposition at the centromere, this does not rule out a role for the centromeric transcripts themselves. To investigate this further we aim to dissect the roles of transcription and RNA transcripts using CRISPR/Cas9 genome editing and other molecular tools by specifically inhibiting transcription and removing RNAs at centromeric loci while monitoring the physiological consequences. Furthermore, we will purify nascent centromeric RNA transcripts, match them to the underlying centromeric DNA and identify potential binding partners. This work will be performed using Drosophila tissue culture cells as an ideal model system for simple centromeres.
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Funding Notes
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References
1. Stirpe, A., and Heun, P. (2022). The ins and outs of CENP-A: Chromatin dynamics of the centromere-specific histone. Semin Cell Dev Biol., 10.1016/j.semcdb.2022.04.003.
2. Bobkov, G.O.M., Huang, A., van den Berg, S.J.W., Mitra, S., Anselm, E., Lazou, V.,
Schunter, S., Federle, R., Imhof, A., Lusser, A., Jansen, ET., and Heun P.,
Spt6 is a maintenance factor for centromeric CENP-A. 2020 Nature
communications, 11(1), 2919. https://doi.org/10.1038/s41467-020-16695-7.
PMID: 32522980
3. Bobkov G, Gilbert N and Heun P, Centromere transcription allows CENP-A to transit from chromatin association to stable incorporation. J Cell Biol 2018, 217: 1957-1972