2026-06-30T03:03:34Zhttps://repisalud.isciii.es/rest/oai/requestoai: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
Repisalud
author
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
funder
Ministerio de Economía y Competitividad (España)
funder
Comunidad de Madrid (España)
funder
Regional Government of Andalusia (España)
funder
Pablo de Olavide University (España)
funder
Heart and Stroke Foundation (Canadá)
funder
Operational Funds from the Hospital for Sick Children
funder
Natural Sciences and Engineering Research Council (Canada)
funder
Canadian Institutes of Health Research
funder
Fundación ProCNIC
funder
Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
2017-10-20T10:23:10Z
2017-10-20T10:23:10Z
2017
PLoS Genet. 2017; 13(8):e1006985
10.1371/journal.pgen.1006985
1553-7404
Plos Genetics
28846746
http://hdl.handle.net/20.500.12105/5102
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.
eng
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
journal article
URL
https://repisalud.isciii.es/bitstreams/82475df6-261c-484a-9584-2238ad7c9e20/download
File
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a58b4afa9d3d182aeebe82dfd00c7cd3
21354197
application/pdf
CTCFCounter-regulAtesCardiomyocyte_2017
URL
https://repisalud.isciii.es/bitstreams/8cce1915-278f-4eda-ac0c-fa9b8a376b6a/download
File
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2f178f27c02333052ac7cff887af8536
79464
text/plain
CTCFCounter-regulAtesCardiomyocyte_2017.txt