Doctoral theses
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| Identifier |
uch.biology.phd//2005kouskouti |
| Title |
Ρόλος των τροποποιήσεων ιστονών και της μεθυλίωσης του TAF10 στη μεταγραφή |
| Alternative Title |
The role of histone modifications and methylation of TAF10 in transcription |
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Author
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Κουσκούτη, Αντιγόνη
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Thesis advisor
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Παπαματθαιάκης, Ιωσήφ
Χαλεπάκης, Γεώργιος
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| Abstract |
SET9 is a member of the SET domain-containing histone methyltransferase family that can specifically methylate histone-3 at lysine 4 position. Although nucleosomal histones are poor substrates for SET9, the active enzyme can stimulate activatorinduced transcription. In the fisrst part of this studied, its shown that SET9 can monomethylate the TBP-associated factor TAF10 at a single lysine residue located at the loop-2 region within the putative histone-fold domain of the protein. Methylated TAF10 has an increased affinity for RNA polymerase II, pointing to a direct role of this modification in preinitiation complex formation. Reporter assays and studies on TAF10-null F9 cells expressing a methylation-deficient TAF10 mutant revealed that SET9-mediated methylation of TAF10 potentiates transcription of some, but not all TAF10-dependent genes. This gene specificity correlated with SET9 recruitment. The promoter-specific effects of SET9-methylated TAF10 may have important implications regarding the biological function of SET domain-containing lysine methylases, whose primary targets have been presumed to be histones. In the second part various histone modifications are examined across the promoter and the coding regions of constitutively active hepatic genes in G0/G1-enriched, mitotically arrested and α-amanitin-blocked cells. Gene activation correlated with localized histone hyperacetylation, H3-K4 tri- or di-methylation and H3-K79 dimethylation and localized nucleosome remodeling at the promoter and the 5 portion of the coding regions. Nucleosomes at more downstream locations were mono-methylated at H3-K4. CBP, PCAF, Brg-1, SNF2H and FACT were recruited to the coding regions in a gene-specific manner, in a similarly restricted promoterproximal pattern. Elongator, however, associated with the more downstream regions. While all factors were dissociated from the chromatin after transcriptional inactivation by α-amanitin, the histone modifications remained stable. In mitotic cells, histone modifications on parental nucleosomes were preserved and were re-generated in a transcription-dependent manner at the newly-deposited nucleosomes, as the cells entered the next G1 phase. The findings suggest that histone modifications may function as molecular memory bookmarks for previously active locations of the genome, thus contributing to the maintenance of active chromatin states through cell division.
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| Language |
Greek |
| Issue date |
2005-12-20 |
| Collection
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School/Department--School of Sciences and Engineering--Department of Biology--Doctoral theses
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Type of Work--Doctoral theses
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| Permanent Link |
https://elocus.lib.uoc.gr//dlib/c/8/d/metadata-dlib-2005kouskouti.tkl
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| Views |
305 |
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