GECS Seminar: Patrick Heun "Epigenetic inheritance and maintenance of centromere identity"
| Dates: | 11 October 2018 |
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| Times: | 13:00 - 14:00 |
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| What is it: | Seminar |
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| Organiser: | Faculty of Biology, Medicine and Health |
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| Who is it for: | University staff |
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| Speaker: | Patrick Heun |
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Gene Expression, Chromatin and Signalling Seminar Programme Autumn 2018
Host: Dave Gerrard
Speaker: Dr Patrick Heun, University of Edinburgh
Abstract:
Centromeres are specific chromatin domains essential for genome stability and proper segregation of mitotic chromosomes. In mitosis, centromeres constitute the chromatin foundation for the kinetochore, a multi-protein complex that mediates the attachment of the sister chromatids to the mitotic spindle. Centromeric identity is defined and inherited in most organisms by an epigenetic mechanism based on the incorporation of a centromere-specific histone H3 variant (CENP-A/cenH3/CID). We find that in fly tissue culture cells that centromeres are transcribed in Drosophila from mitosis into G1, which temporally coincides with the deposition of new dCENP-A. Interestingly, transcriptional inhibition prevents full chromatin incorporation of new dCENP-A, although an initial recruitment of new dCENP-A to centromeres is unaffected. As transcription is able to expel nucleosomes from DNA, we propose that transcription is repurposed at the centromere for the removal of ‘placeholder’ nucleosomes. However, this also implies that transcription poses a potential danger to epigenetic centromere identity due to the unintentional eviction of old dCENP-A nucleosomes. We found that loss of parental dCENP-A is counteracted the transcription elongation factor and histone chaperone Spt6 that we recently found to be associated with dCENP-A. Localization of Spt6 to centromeres is largely restricted to mitosis and G1 and a lower salt sensitivity indicates that it binds dCENP-A with higher specificity than canonical histone H3. In the genome, Spt6 is known to prevent transcription-coupled loss of nucleosomes through nucleosome re-incorporation. Accordingly, parental dCENP-A nucleosomes are specifically lost in Spt6 depleted cells during the dCENP-A loading process indicating that the ability of Spt6 to recycle expelled nucleosomes is required for the long-term stability of the centromeric mark. Therefore, Spt6 is a dCENP-A maintainance factor and centromeric transcription and Spt6 co-operate to ensure stable inheritance of dCENP-A at the centromere.
Speaker
Patrick Heun
Role: Dr
Organisation: Wellcome Centre for Cell Biology, University of Edinburgh
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Michael Smith Lecture Theatre
Michael Smith Building
Manchester
