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Marc Weber

About Marc Weber:
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SEEK ID: https://fairdomhub.org/people/1010

Location:  Spain

Expertise: Not specified

Tools: Not specified

ORCID: https://orcid.org/0000-0001-7920-5655

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Related items

MycoSynVac - Engineering Mycoplasma pneumoniae as a broad-spectrum animal vaccine

The MycoSynVac project AIMS at using cutting-edge synthetic biology methodologies to engineer Mycoplasma pneumoniae as a universal chassis for vaccination.
Designing a universal Mycoplasma chassis that can be deployed as single- or multi-vaccine in a range of animal hosts. Annually, infections caused by Mycoplasma species in poultry, cows, and pigs result in multimillion Euro losses in the USA and Europe.
There is no effective vaccination against many Mycoplasmas that infect pets, humans and farm
...

Programme: Independent Projects

Public web page: http://www.mycosynvac.eu/

CRG Centre for Genomic Regulation

Country:  Spain

City: Barcelona

Web page: http://www.crg.eu/

A context-specific cardiac β-catenin and GATA4 interaction influences TCF7L2 occupancy and remodels chromatin driving disease progression in the adult heart
GMDS Project Group "FAIRe Dateninfrastrukturen für die Biomedizinische Informatik"

Abstract (Expand)

Chromatin remodelling precedes transcriptional and structural changes in heart failure. A body of work suggests roles for the developmental Wnt signalling pathway in cardiac remodelling. Hitherto, there … is no evidence supporting a direct role of Wnt nuclear components in regulating chromatin landscapes in this process. We show that transcriptionally active, nuclear, phosphorylated(p)Ser675-β-catenin and TCF7L2 are upregulated in diseased murine and human cardiac ventricles. We report that inducible cardiomyocytes (CM)-specific pSer675-β-catenin accumulation mimics the disease situation by triggering TCF7L2 expression. This enhances active chromatin, characterized by increased H3K27ac and TCF7L2 occupancies to cardiac developmental and remodelling genes in vivo. Accordingly, transcriptomic analysis of β-catenin stabilized hearts shows a strong recapitulation of cardiac developmental processes like cell cycling and cytoskeletal remodelling. Mechanistically, TCF7L2 co-occupies distal genomic regions with cardiac transcription factors NKX2–5 and GATA4 in stabilized-β-catenin hearts. Validation assays revealed a previously unrecognized function of GATA4 as a cardiac repressor of the TCF7L2/β-catenin complex in vivo, thereby defining a transcriptional switch controlling disease progression. Conversely, preventing β-catenin activation post-pressure-overload results in a downregulation of these novel TCF7L2-targets and rescues cardiac function. Thus, we present a novel role for TCF7L2/β-catenin in CMs-specific chromatin modulation, which could be exploited for manipulating the ubiquitous Wnt pathway.

Authors: Lavanya M Iyer, Sankari Nagarajan, Monique Woelfer, Eric Schoger, Sara Khadjeh, Maria Patapia Zafiriou, Vijayalakshmi Kari, Jonas Herting, Sze Ting Pang, Tobias Weber, Franziska S Rathjens, Thomas H Fischer, Karl Toischer, Gerd Hasenfuss, Claudia Noack, Steven A Johnsen, Laura C Zelarayán

Date Published: 6th Apr 2018

Publication Type: Not specified

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