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Cardiac chromatin biology / Kardiale Chromatinbiologie

 

Organization layers
Figure: Scheme of the different epigenetic and chromatin organization layers (Gilsbach & Hein)

Cardiac chromatin biology and functional epigenomics

 
Background

The heart is a highly specialized organ consisting of different cell-types, including cardiac myocytes, each with specific functions. Different layers of epigenetic mechanisms coordinate the transcriptional activity of each cell. This ensures cell type specific gene expression as well as execution of gene expression programs crucial for development and progression of heart diseases. DNA and histone modifications are key factors regulating the accessibility of the DNA for binding proteins. This includes transcription factors as well as the RNA polymerase. The three-dimensional organization of the genome enables interaction between distal transcription factor binding sites (enhancer) and gene promoters. These enhancer promoter contacts are the most specific regulatory mechanisms of the genome and are likely the basis for cell-type diversity in metazoans. However, the relevance of individual chromatin contacts for transcriptional control in development and disease is largely unknown. These contacts are embedded into higher order hierarchical chromatin structures ensuring packing of the genome into a tiny nucleus while maintaining the critical parts in an open conformation.

Methods

To resolve these different layers of chromatin biology in cardiac cell types we apply state of the art molecular biology, epigenetic and cell sorting techniques in combination with massive parallel sequencing. Computational methods are a central part of our research, since they translate the generated sequencing data into genome-wide high-resolution maps. Combining multiple layers of epigenetic information, including histone modifications, DNA methylation, chromatin organization and gene expression, allows us to identify potential regulatory elements in development, health and disease of cardiac cells. To prove the functional relevance of annotated regulatory regions we combine CRISPR-based functional genomics with single cell technology.

This approach enables us to address a central question of cardiac biology:

How does the epigenome control transcriptional activity in development and disease of cardiac cell-types.

Team: Ralf Gilsbach, Martin Schwaderer, Rebecca Bednarz
Alumni: Stephan Nothjunge (now FMI, Basel)
Contact: Ralf Gilsbach (Ralf.Gilsbach[at]pharmakol.uni-freiburg.de)

Selected publications:
Gilsbach et al., Nat. Commun., 2018
Nothjunge et al., Gilsbach, Nat. Commun., 2017
Gilsbach et al., Nat. Commun., 2014
Mayer*, Gilsbach* et al., Circ. Res., 2015
Preißl et al., Gilsbach, Circ. Res., 2015

Funding: DFG Deutsche Forschungsgemeinschaft, BW Stiftung (Programm Epigenetik)

Genomic snapshot
Figure: Representative genomic snapshot of chromatin organization and epigenetic modifications in adult cardiac myocytes (http://cardiacepigenome.org/)

 

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