The Isl1/Ldb1 Complex Orchestrates Genome-wide Chromatin Organization to Instruct Differentiation of Multipotent Cardiac Progenitors
Caputo L, Witzel HR, Kolovos P, Cheedipudi S, Looso M, Mylona A, Van Ijcken WFJ, Laugwitz KL, Evans SM, Braun T, Soler E, Grosveld F, Dobreva G (2015)
Publication Type: Journal article
Publication year: 2015
Journal
Book Volume: 17
Pages Range: 287-299
Article Number: 1833
Journal Issue: 3
DOI: 10.1016/j.stem.2015.08.007
Abstract
Cardiac stem/progenitor cells hold great potential for regenerative therapies; however, the mechanisms regulating their expansion and differentiation remain insufficiently defined. Here we show that Ldb1 is a central regulator of genome organization in cardiac progenitor cells, which is crucial for cardiac lineage differentiation and heart development. We demonstrate that Ldb1 binds to the key regulator of cardiac progenitors, Isl1, and protects it from degradation. Furthermore, the Isl1/Ldb1 complex promotes long-range enhancer-promoter interactions at the loci of the core cardiac transcription factors Mef2c and Hand2. Chromosome conformation capture followed by sequencing identified specific Ldb1-mediated interactions of the Isl1/Ldb1 responsive Mef2c anterior heart field enhancer with genes that play key roles in cardiac progenitor cell function and cardiovascular development. Importantly, the expression of these genes was downregulated upon Ldb1 depletion and Isl1/Ldb1 haplodeficiency. In conclusion, the Isl1/Ldb1 complex orchestrates a network for heart-specific transcriptional regulation and coordination in three-dimensional space during cardiogenesis.
Involved external institutions
Max Planck Institute for Heart and Lung Research / Max-Planck-Institut für Herz- und Lungenforschung
Germany (DE)
Erasmus University Medical Center (MC)
Netherlands (NL)
Technische Universität München (TUM)
Germany (DE)
University of California, San Diego
United States (USA) (US)
Germany (DE)
Erasmus University Medical Center (MC)
Netherlands (NL)
Technische Universität München (TUM)
Germany (DE)
University of California, San Diego
United States (USA) (US)
How to cite
APA:
Caputo, L., Witzel, H.R., Kolovos, P., Cheedipudi, S., Looso, M., Mylona, A.,... Dobreva, G. (2015). The Isl1/Ldb1 Complex Orchestrates Genome-wide Chromatin Organization to Instruct Differentiation of Multipotent Cardiac Progenitors. Cell Stem Cell, 17(3), 287-299. https://doi.org/10.1016/j.stem.2015.08.007
MLA:
Caputo, Luca, et al. "The Isl1/Ldb1 Complex Orchestrates Genome-wide Chromatin Organization to Instruct Differentiation of Multipotent Cardiac Progenitors." Cell Stem Cell 17.3 (2015): 287-299.
BibTeX: Download