Please select the desired project time frame:

• July 2026
• January 2026
• July 2025
• January 2025
• July 2024
• January 2024
• July 2023
• January 2023
• July 2022
• January 2022
• July 2021
• January 2021
• July 2020
• January 2020
• July 2019
• January 2019
• July 2018
• January 2018
• July 2017
• January 2017
• July 2016
• January 2016
• July 2015
• January 2015
• July 2014
• January 2014
• July 2013
• January 2013
• July 2012
• January 2012
• July 2011
• January 2011
• July 2010
• January 2010
• July 2009
• January 2009
• July 2008
• January 2008
• July 2007
• January 2007
• July 2006
• January 2006
• July 2005
• January 2005
• July 2004
• January 2004
• July 2003
• January 2003
• July 2002
• January 2002
• July 2001
• January 2001

Start of funding 01.01.2008

Novel Genomics Technologies to Screen for Targets of Cardiac Transcription Factors

---

Cardiogenic factors of the NK homeodomain and T-box families have essential functions during heart development, are conserved from Drosophila to man, and are also involved in human congenital heart diseases. The goal of this collaborative project is to use the advantages of the genetic model organism Drosophila to perform genome-wide screens for targets of key representatives of these transcription factor families that play pivotal roles in heart development. For this purpose, we will perform chromatin immunoprecipitations from embryos of different stages during cardiogenesis. The precipitated DNA fragments will be analyzed on tiled genomic microarrays and with alternative genome-wide screening methods in order to identify potential genomic target sites of these factors. The bioinformatics and functional characterization of these target sites and genes will provide us with a better understanding of the regulation of heart development.

Final report:
The Drosophila homeodomain protein Tinman was the first transcription factor found to control the development and differentiation of the heart in any species. In this project, we addressed the question of which are the downstream target genes of Tinman that are necessary to exert its cardiogenic functions. We have performed a genome-wide analysis of DNA regions associated with Tinmanbinding in embryos and the genes linked to them by Chromatin immunoprecipitations (ChIP-chip) (Jin et al., 2013). The combined data from our in-depth in vivo assays of sequence elements with high Tinman occupancy allowed the following general conclusions: (1) The majority of such sequences are active as regulatory elements (called enhancers) in mesodermal tissues that include Tinmanexpressing cells. (2) The enhancers active in the heart progenitor cells and the heart generally are dependent on tinman gene activity, whereas those active in non-cardiac mesoderm are often bound neutrally by Tinman. (3) Tinman binding motifs in most cases are essential for cardiac enhancer activity, but in some cases they can be functionally-redundant with those of other cardiogenic factors. (4) Tinman-occupied cardiac enhancers are enriched for a newly-discovered binding motif for an unknown factor that is functional in vivo.

Jin, H., Stojnic, R., Adryan, B., Ozdemir, A., Stathopoulos, A., Frasch, M., 2013. Genome-wide screens for in vivo Tinman binding sites identify cardiac enhancers with diverse functional architectures. PLoS Genet. 9, e1003195.