2026-06-30T03:04:00Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/51022024-09-27T07:58:01Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607

00925njm 22002777a 4500 dc Gomez-Velazquez, Melisa author Badia-Careaga, Claudio author Lechuga-Vieco, Ana V. author Nieto-Arellano, Rocio author Tena, Juan J. author Rollan, Isabel author Alvarez, Alba author Torroja, Carlos author Caceres, Eva F. author Roy, Anna author Galjart, Niels author Delgado-Olguin, Paul author Sanchez-Cabo, Fatima author Enriquez, Jose Antonio author Luis Gomez-Skarmeta, Jose author Manzanares, Miguel author 2017 Cardiac progenitors are specified early in development and progressively differentiate and mature into fully functional cardiomyocytes. This process is controlled by an extensively studied transcriptional program. However, the regulatory events coordinating the progression of such program from development to maturation are largely unknown. Here, we show that the genome organizer CTCF is essential for cardiogenesis and that it mediates genomic interactions to coordinate cardiomyocyte differentiation and maturation in the developing heart. Inactivation of Ctcf in cardiac progenitor cells and their derivatives in vivo during development caused severe cardiac defects and death at embryonic day 12.5. Genome wide expression analysis in Ctcf mutant hearts revealed that genes controlling mitochondrial function and protein production, required for cardiomyocyte maturation, were upregulated. However, mitochondria from mutant cardiomyocytes do not mature properly. In contrast, multiple development regulatory genes near predicted heart enhancers, including genes in the IrxA cluster, were downregulated in Ctcf mutants, suggesting that CTCF promotes cardiomyocyte differentiation by facilitating enhancer-promoter interactions. Accordingly, loss of CTCF disrupts gene expression and chromatin interactions as shown by chromatin conformation capture followed by deep sequencing. Furthermore, CRISPR-mediated deletion of an intergenic CTCF site within the IrxA cluster alters gene expression in the developing heart. Thus, CTCF mediates local regulatory interactions to coordinate transcriptional programs controlling transitions in morphology and function during heart development. PLoS Genet. 2017; 13(8):e1006985 10.1371/journal.pgen.1006985 1553-7404 Plos Genetics 28846746 http://hdl.handle.net/20.500.12105/5102 GENE-EXPRESSION TRANSCRIPTION FACTORS NEURAL DEVELOPMENT DNA INTERACTIONS HUMAN GENOME HUMAN-CELLS MITOCHONDRIAL ORGANIZATION MAP DIFFERENTIATION CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart