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

Biology Open
Christiane FuchsG Weitzer

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.

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Citations

Dec 3, 2017·Cold Spring Harbor Perspectives in Biology·Elly M Hol, Yassemi Capetanaki
Apr 24, 2018·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Cynthia YeungAdrian Baranchuk
Jul 22, 2018·Biophysics Reviews·Mary TsikitisYassemi Capetanaki
Jan 22, 2021·Cytoskeleton·Ecem Kural-Mangıt, Pervin Rukiye Dinçer
Apr 5, 2021·Biochemical and Biophysical Research Communications·Keigo MurakamiKuniyuki Hatori
Apr 8, 2021·The FEBS Journal·Giulio AgnettiShenhav Cohen
May 1, 2021·International Journal of Molecular Sciences·Lorenzo MaggiGiovanna Lattanzi

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Methods Mentioned

BETA
ChIP
transfection
fluorescence microscopy
flow cytometry
FACS
PCR
pull-down
immunoprecipitation

Software Mentioned

Photoshop
Adobe Photoshop
NetNES
FlowJo

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