CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart

• DOI: 10.1371/journal.pgen.1006985
• Publication Date: 2017-08-28T13:33:34Z
• Authors: Melisa Gomez-Vela...; Claudio Badia-Car...; Ana Victoria Lech...; Rocio Nieto-Arellano; Juan J. Tena; Isabel Rollan; Alba Alvarez; Carlos Torroja; Eva F. Caceres; Anna R. Roy; Niels Galjart; Paul Delgado-Olguin; Fatima Sanchez-Cabo; Jose Antonio Enri...; Jose Luis Gomez-S...; Miguel Manzanares
• Keywords: CTCF; Heart development

Cardiac progenitors are specified early in development and progressively differentiate mature into fully functional cardiomyocytes. This process is controlled by an extensively studied transcriptional program. However, the regulatory events coordinating progression of such program from to maturation largely unknown. Here, we show that genome organizer CTCF essential for cardiogenesis it mediates genomic interactions coordinate cardiomyocyte differentiation developing heart. Inactivation Ctcf cardiac progenitor cells their derivatives vivo during caused severe defects death at embryonic day 12.5. Genome wide expression analysis mutant hearts revealed genes controlling mitochondrial function protein production, required maturation, were upregulated. mitochondria cardiomyocytes do not properly. In contrast, multiple near predicted heart enhancers, including IrxA cluster, downregulated mutants, suggesting promotes facilitating enhancer-promoter interactions. Accordingly, loss disrupts gene chromatin as shown conformation capture followed deep sequencing. Furthermore, CRISPR-mediated deletion intergenic site within cluster alters Thus, local programs transitions morphology development.