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|Title: ||“Silencing the ribosomal locus of Saccharomyces cerevisiae: role of RNA polymerase I transcription and chromatin acetylation”|
|Authors: ||CESARINI, ELISA|
|Tutor: ||Camilloni, Giorgio|
|Issue Date: ||25-Jan-2011|
|Abstract: ||During my PhD I investigated the transcriptional silencing occurring at the ribosomal DNA of
In yeast the ribosomal locus (rDNA) is transcribed with high efficiency by RNA polymerase I (Pol I) and
III to synthetize ribosomal RNAs.
It has been discovered that RNA polymerase Pol II (Pol II) can also transcribe the ribosomal locus, at low
level, starting from cryptic promoters and generating non coding RNAs (ncRNAs). ncRNA transcription
leads to genome instability, measurable as extrachromosomal rDNA circles (ERCs) accumulation.
I studied the effect of Pol I transcription in the synthesis of ncRNA and in the rDNA chromatin structure,
employing yeast mutants differing in the Pol I transcriptional rate in order to find whether correlations exist
between Pol I activity and ncRNA synthesis.
I found that RNA polymerase I transcription is required to repress Pol II activity within rDNA. In Pol I
transcription mutants the synthesis of ncRNA is strongly enhanced and histone H3 and H4 acetylation
appears at the Pol II cryptic promoters. Morover, I described how nucleosome spacing and structure respond
differently to Pol I and Pol II transcription within the ribosomal gene cluster.
As post-doc I found that histone deacetylases (Rpd3p and Hst3p) and high mobility group proteins (Nhp6a
and b) regulate the rate of ncRNA and ERCs production at rDNA. Surprisingly every of these mutants has
an altered level of histone H4 lysine 16 (H4K16) acetylation.
The key role of this residue in the co-ordination of transcription and recombination at rDNA was further
demonstrated employing yeast strains characterized by histone H4K16Q/R substitutions.|
|Appears in PhD:||SCIENZE PASTEURIANE|
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|Cesarini et al., Eukaryotic cell 2010.pdf||Pubblicazione scientifica||1.37 MB||Adobe PDF|
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