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| Status |
Public on Jul 30, 2013 |
| Title |
PAX5 overexpression is not enough to reestablish the mature B-cell phenotype in classical Hodgkin lymphoma (ChIP-Seq) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
In lymphomas derived from mature B cells the expression of the transcription factor PAX5 is maintained whereas classical Hodgkin lymphoma displays significantly reduced PAX5 expression despite its derivation from mature B cells. To elucidate the functional role of PAX5 in classical Hodgkin lymphoma, we re-established the PAX5 expression in the Hodgkin cell line L428 with and without epigenetic modulation. To this end, we stably transfected the Hodgkin cell line L428 with an inducible PAX5 expression construct. Although the overexpressed PAX5 was transcriptionally active as demonstrated by synthetic reporter constructs, no induction of the B-cell phenotype was achieved. PAX5 chromatin immunoprecipitation with subsequent next generation sequencing in B-cell lines and the PAX5 overexpressing L428 cell line showed different binding patterns. Since epigenetic restrictions might affect PAX5 binding, combined DNA demethylation and histone acetylation was performed. However, no re-expression of B-cell genes was observed also under these conditions. Thus, PAX5 is not sufficient for the re-activation of the B-cell program in Hodgkin cells despite epigenetic opening of the chromatin. This clearly indicates that the repression of the B-cell identity of the Hodgkin cells is caused and secured by complex molecular mechanisms.
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| Overall design |
Analysis of genome-wide PAX5 binding sites in B-cell lines (Raji, Namalwa) and the PAX5-producing Hodgkin cell line L428-PAX5 by ChIP-Seq
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| Contributor(s) |
Dimitrova L, Seitz V, Hecht J, Lenze D, Hansen P, Szczepanowski M, Ma L, Oker E, Sommerfeld A, Jundt F, Klapper W, Hummel M |
| Citation(s) |
23842424 |
| Submission date |
Feb 21, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Lora Dimitrova |
| E-mail(s) |
lora.dimitrova@charite.de
|
| Organization name |
Charité-University Medicine Berlin
|
| Department |
Institute of Pathology
|
| Street address |
Hindenburgdamm 30
|
| City |
Berlin |
| State/province |
Berlin |
| ZIP/Postal code |
12200 |
| Country |
Germany |
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| Platforms (1) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
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| Samples (12)
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| Relations |
| SRA |
SRP018781 |
| BioProject |
PRJNA190710 |
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