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URN: urn:nbn:de:bsz:25-opus-10356
URL: http://www.freidok.uni-freiburg.de/volltexte/1035/

Kolanczyk, Mateusz

Molecular analysis of transcriptional properties of Pbx1 and E2a-Pbx1

Molekulare analyse von transkriptionellen eigenschaften der Pbx1 und E2a-Pbx1 gene

Dokument1.pdf (4.784 KB) (md5sum: e163db3232a3ca2214d5cabcdabb22ed)

Kurzfassung in Englisch

E2a-Pbx1 is an oncogene formed by the t(1;19) chromosomal translocation, which is found in 20% of pediatric pre-B acute lymphoblastic leukemias. E2a-Pbx1 joins exons encoding the amino-terminal transactivation domain of E2a with those encoding the carboxyterminal homeodomain of Pbx1, which binds 5’-TGAT-3’ (3’-ATCA-5’) elements. While E2a-Pbx1 can activate transcription through homodimer elements (TGATTGAT) or through heterodimer elements (e.g. TGATTAAT) with Hox proteins in transcription reporter constructs. The mechanisms by which it activates target gene transcription in vivo have not been explored extensively. Here we identify E2a-Pbx1 responsive sequence in EF-9 promoter.
We also report that LDFS transcriptional activation motif of E2a is essential for transactivation of EF-9, but dispensable for activation of FGF15 target genes in NIH3T3 fibroblasts. Furthermore the LDFS motif of E2a is essential for inducing proliferation of NIH3T3 fibroblasts but dispensable for blocking differentiation of myeloid progenitors. These data suggest that E2a-Pbx1 activates its multiple target genes by at least two mechanisms and that different subsets of its target genes mediate different subsets of its transforming properties.

Pbx1 is a homeodomain transcription factor involved in execution of HOX protein
mediated developmental program of gene expression. Recently Pbx1 knock-out mice were reported to die in the gestation day 15-16, with the severe hypoplasia or aplasia of multiple organs. Utilizing the Cre-loxP system we inactivated both alleles of the Pbx1 gene in the ES cells and mice. We induced neural differentiation of the wild-type and Pbx1 knockout ES cells by aggregation and Retinoic Acid (RA) induction. In order to check for gene expression changes during differentiation we collected RNA material from cultured cells up to the day 9 after reattachment of the embryoid bodies (EB) to the adhesive media. Parallel with observation of intensified neural and glial gene

SWD-Schlagwörter: Transkription , Proteine , Chromatin
Institut: Institut für Biologie 2
Fakultät: Fakultät für Biologie (bis Sept. 2002)
DDC-Sachgruppe: Biowissenschaften, Biologie
Dokumentart: Dissertation
Erstgutachter: Neuhaus, Gunther (Prof. Dr.)
Sprache: Englisch
Tag der mündlichen Prüfung: 12.11.2003
Erstellungsjahr: 2003
Publikationsdatum: 18.11.2003