LYMPHOCONTROL
Transcriptional networks controlling lymphocyte development
| Coordinatore | FORSCHUNGSINSTITUT FUER MOLEKULARE PATHOLOGIE Ges.m.b.H
Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie. |
| Nazionalità Coordinatore | Austria [AT] |
| Totale costo | 2˙499˙305 € |
| EC contributo | 2˙499˙305 € |
| Programma | FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | ERC-2011-ADG_20110310 |
| Funding Scheme | ERC-AG |
| Anno di inizio | 2012 |
| Periodo (anno-mese-giorno) | 2012-07-01 - 2017-06-30 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
FORSCHUNGSINSTITUT FUER MOLEKULARE PATHOLOGIE Ges.m.b.H
Organization address
address: Dr. Bohr-Gasse 7 contact info |
AT (VIENNA) | hostInstitution | 2˙499˙305.00 |
| 2 |
FORSCHUNGSINSTITUT FUER MOLEKULARE PATHOLOGIE Ges.m.b.H
Organization address
address: Dr. Bohr-Gasse 7 contact info |
AT (VIENNA) | hostInstitution | 2˙499˙305.00 |
Mappa
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Obiettivo del progetto (Objective)
'Acquired immunity to foreign pathogens depends on functional B and T cells. The objective of this proposal is to elucidate the transcriptional control of lymphocyte development at three stages by deciphering the transcriptional networks specifying pro-B and pro-T cells in early lymphopoiesis and plasma cells in terminal B cell differentiation. To this end, we generated knock-in mice carrying a biotin acceptor sequence at the C-terminus of transcription factors, which can be biotinylated by transgenic co-expression of the E. coli biotin ligase BirA. In vivo biotinylation facilitates antibody-independent precipitation of these transcription factors by streptavidin pulldown (Bio-ChIP). Preliminary Bio-ChIP sequencing experiments validated this approach for genome-wide identification of transcription factor target genes. Bio-ChIP sequencing will be used to identify the target genes of key transcription factors controlling the development of pro-B cells (Ikaros, E2A, STAT5, EBF1, Pax5, PU.1, IRF4), pro-T cells (Notch1, RBP-Jï«, GATA3, Ikaros, E2A, STAT5) and plasma cells (Blimp1, IRF4, XBP1). RNA sequencing of wild-type and mutant lymphocytes will determine the regulated target genes of these factors, which are ultimately relevant for the elucidation of transcriptional networks. The function of selected target genes at central nodes of these networks will be analyzed by the latest miR30-shRNA knockdown technology. Finally, regulatory complexes interacting with these transcription factors will be identified by streptavidin-pulldown purification and mass spectrometry followed by their integration into the transcriptional networks by ChIP-seq mapping to the transcription factor target genes. These experiments will provide fundamentally new molecular insight into the generation of all three lymphocyte stages and will contribute to a better understanding of how deregulation of the transcriptional control promotes the development of lymphoid malignancies.'