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Pax3 defines a new pathway at pericentric heterochromatin
Manuela Scaranaro
Art der Arbeit
Dissertation
Universität
Universität Wien
Fakultät
Fakultät für Lebenswissenschaften
Betreuer*in
Thomas Jenuwein
DOI
10.25365/thesis.5082
URN
urn:nbn:at:at-ubw:1-29082.48859.448065-7
Link zu u:search
(Print-Exemplar eventuell in Bibliothek verfügbar)
Abstracts
Abstract
(Deutsch)
The association between DNA and histones gives rise to chromatin. In interphase cells there are two different kinds of chromatin: euchromatin and heterochromatin. Pericentric heterochromatin represents the vast majority of the heterochromatin and several features allow to distinguish it from the rest of the chromatin. Pericentric heterochromatin is characterized by a repetitive DNA sequence: in mouse a 234 bp motif (major satellite) is present around 10´000 times in every chromosome. One of the first events that takes place there is the transcription of the major satellites and the subsequent formation of dsRNA. Thereafter, some proteins (such as Suv39h enzymes and HP1α) and histone posttranslational modifications (H3K9me3 and H4K20me3) are enriched there.
Pax3 is a protein so far very well characterized for its developmental role. By EGFP-tagging, it was observed that, like a few other proteins, Pax3 localizes at pericentric heterochromatin in mouse fibroblasts and its accumulation there is Suv39h-independent: Pax3 recognizes, by its homeodomain, a palindromic sequence of the second subrepeat of the major satellite. Fibroblasts, where only a truncated Pax3 is expressed have been generated: this truncated protein cannot bind the major satellite and therefore it mimics a knockout. In Pax3 null cells repressive histone methylation is reduced and the amount of transcripts (dsRNA and ssRNA) generated from the major satellites increases. The data generated suggest that it is indeed the local increase of the amount of ssRNA and dsRNA to be the cause of the reduction of H3K9me3, H4K20me3 and H3K27me1 that usually decorate pericentric heterochromatin.
Pax3 pericentric localization defines a novel pathway: transcription of the major satellites needs to be repressed by developmental regulators in order to establish heterochromatin (Scaranaro et al., submitted).
In this thesis in addition we will ask whether dsRNA can be a modulator of HMTase activity and it will be shown that mapping new Su(var) genes in Drosophila allows to discover new pericentric components in other species too.
Schlagwörter
Schlagwörter
(Deutsch)
Pax3 heterochromatin transkripzion
Autor*innen
Manuela Scaranaro
Haupttitel (Englisch)
Pax3 defines a new pathway at pericentric heterochromatin
Publikationsjahr
2009
Umfangsangabe
111 S. : Ill., graph. Darst.
Sprache
Englisch
Beurteiler*innen
Gunter Reuter ,
Meinrad Busslinger
Klassifikation
30 Naturwissenschaften allgemein > 30.00 Naturwissenschaften allgemein: Allgemeines
AC Nummer
AC05040840
Utheses ID
4536
Studienkennzahl
UA | 091 | 490 | |