SPLICE

Molecular mechanisms of transcriptional regulation of lymphocyte development by the E2A splice variants E12 and E47

Coordinatore	UNIVERSITAETSKLINIKUM FREIBURG    more  Organization address address: HUGSTETTER STRASSE 49 city: FREIBURG postcode: 79106 contact info Titolo: Mr. Nome: Jürgen Cognome: Dreyer Email: send email Telefono: 4976130000000 Fax: 4976130000000
Nazionalità Coordinatore	Germany [DE]
Totale costo	100˙000 €
EC contributo	100˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2010-RG
Funding Scheme	MC-IRG
Anno di inizio	2011
Periodo (anno-mese-giorno)	2011-03-01   -   2015-06-10

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITAETSKLINIKUM FREIBURG  Organization address address: HUGSTETTER STRASSE 49 city: FREIBURG postcode: 79106 contact info Titolo: Mr. Nome: Jürgen Cognome: Dreyer Email: send email Telefono: 4976130000000 Fax: 4976130000000	DE (FREIBURG)	coordinator	100˙000.00

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 Obiettivo del progetto (Objective)

'The E2A gene encodes for two alternatively spliced proteins, namely E12 and E47, which belong to the family of basic helix-loop-helix transcription factors. The E2A proteins have been characterized extensively as regulators during various stages of B and T lymphocyte development. Recently, we have generated mice deficient for either E12 or E47 and examined their roles in B cell maturation. We show that E47 is essential for developmental progression at the pre-pro- B cell stage, while E12 is dispensable for early B cell development, commitment and maintenance. In contrast, both E12 and E47 play critical roles in pre-B and immature B cells to promote Igλ germline transcription as well as Igλ VJ gene rearrangement. However, it is unclear which molecular mechanisms are used by E12 and E47 to drive lymphocyte development. Thus, the goals of this study are to 1. identify the signalling events that control transcription and splicing of the E2A gene, 2. define individual target genes and interaction partners of E12 and E47 and 3. to examine the distinct functions for E12 and E47 during T cell development. These goals will be accomplished using the previously generated mouse models, lacking either the E12 or E47 protein in combination with cellular and molecular biology approaches. Additionally, the first goal will be approached in cooperation with the applicant’s previous lab, since this lab has extensive experience with the proposed state-of-the-art whole genome Chromatin Immunoprecipitation combined with deep sequencing (ChIP-Seq) approach. Overall, this project will contribute to our understanding of the molecular mechanisms of transcriptional regulation as well as lymphocyte development.'

Introduzione (Teaser)

During development, cell emergence, differentiation and maturation are tightly regulated by the specific action of various transcription factors. A European study is investigating the function of two highly similar splicing variants of the same gene during lymphocyte development.