Artículo del mes
abril 2022

CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression

Referencia artículo:
Franke M, De la Calle-Mustienes E, Neto A, Almuedo-Castillo M, Irastorza-Azcarate I, Acemel RD, Tena JJ, Santos-Pereira JM*, Gómez-Skarmeta JL. 2021. CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression. Nature Communications 12:5415. *Corresponding author
En este trabajo, hemos utilizado el pez cebra para dilucidar el papel que juega la estructura tridimensional del genoma en la regulación de la expresión de los genes durante el desarrollo embrionario. Para ello, hemos eliminado una proteína llamada CTCF, que es esencial para el plegamiento del genoma. Nuestros resultados muestran que la ausencia de CTCF altera las interacciones entre cientos de genes importantes para el desarrollo y sus elementos reguladores, dando como resultado una desregulación de estos genes y a su vez de los que dependen de ellos.
Resumen
Coordinated chromatin interactions between enhancers and promoters are critical for gene regulation. The architectural protein CTCF mediates chromatin looping and is enriched at the boundaries of topologically associating domains (TADs), which are sub-megabase chromatin structures. In vitro CTCF depletion leads to a loss of TADs but has only limited effects over gene expression, challenging the concept that CTCF-mediated chromatin structures are a fundamental requirement for gene regulation. However, how CTCF and a perturbed chromatin structure impacts gene expression during development remains poorly understood. Here we link the loss of CTCF and gene regulation during patterning and organogenesis in a ctcf knockout zebrafish model. CTCF absence leads to loss of chromatin structure and affects the expression of thousands of genes, including many developmental regulators. Our results demonstrate the essential role of CTCF in providing the structural context for enhancer-promoter interactions, thus regulating developmental genes.
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