title: Desmin enters the nucleus of cardiac stem cells and modulates Nkx2.5 expression by participating in transcription factor complexes that interact with the nkx2.5 gene.
abstract: The transcription factor Nkx2.5 and the intermediate filament protein desmin are simultaneously expressed in cardiac progenitor cells during commitment of primitive mesoderm to the cardiomyogenic lineage. Up-regulation of Nkx2.5 expression by desmin suggests that desmin may contribute to cardiogenic commitment and myocardial differentiation by directly influencing the transcription of the nkx2.5 gene in cardiac progenitor cells. Here, we demonstrate that desmin activates transcription of nkx2.5 reporter genes, rescues nkx2.5 haploinsufficiency in cardiac progenitor cells, and is responsible for the proper expression of Nkx2.5 in adult cardiac side population stem cells. These effects are consistent with the temporary presence of desmin in the nuclei of differentiating cardiac progenitor cells and its physical interaction with transcription factor complexes bound to the enhancer and promoter elements of the nkx2.5 gene. These findings introduce desmin as a newly discovered and unexpected player in the regulatory network guiding cardiomyogenesis in cardiac stem cells.
authors.affiliation: Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, Vienna A1030, Austria.
authors.forename: Christiane
authors.initials: C
authors.lastname: Fuchs
authors.affiliation: Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, Vienna A1030, Austria.
authors.forename: Sonja
authors.initials: S
authors.lastname: Gawlas
authors.affiliation: Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, Vienna A1030, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Heher
authors.affiliation: Center of Basic Research, Biomedical Research Foundation, Academy of Athens, Athens 115 27, Greece.
authors.forename: Sofia
authors.initials: S
authors.lastname: Nikouli
authors.affiliation: Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, Vienna A1030, Austria.
authors.forename: Hannah
authors.initials: H
authors.lastname: Paar
authors.affiliation: Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, Vienna A1030, Austria.
authors.forename: Mario
authors.initials: M
authors.lastname: Ivankovic
authors.affiliation: Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, Vienna A1030, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Schultheis
authors.affiliation: Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, Vienna A1030, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Klammer
authors.affiliation: Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, Vienna A1030, Austria.
authors.forename: Teresa
authors.initials: T
authors.lastname: Gottschamel
authors.affiliation: Center of Basic Research, Biomedical Research Foundation, Academy of Athens, Athens 115 27, Greece.
authors.forename: Yassemi
authors.initials: Y
authors.lastname: Capetanaki
authors.affiliation: Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, Vienna A1030, Austria georg.weitzer@meduniwien.ac.at.
authors.forename: Georg
authors.initials: G
authors.lastname: Weitzer
keywords: Cardiac progenitor cells; Desmin; Intermediate filament protein; Nkx2.5; Nuclear localization; Transcriptional regulation