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Cell ; 186(18): 3826-3844.e26, 2023 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-37536338

RESUMEN

Previous studies have identified topologically associating domains (TADs) as basic units of genome organization. We present evidence of a previously unreported level of genome folding, where distant TAD pairs, megabases apart, interact to form meta-domains. Within meta-domains, gene promoters and structural intergenic elements present in distant TADs are specifically paired. The associated genes encode neuronal determinants, including those engaged in axonal guidance and adhesion. These long-range associations occur in a large fraction of neurons but support transcription in only a subset of neurons. Meta-domains are formed by diverse transcription factors that are able to pair over long and flexible distances. We present evidence that two such factors, GAF and CTCF, play direct roles in this process. The relative simplicity of higher-order meta-domain interactions in Drosophila, compared with those previously described in mammals, allowed the demonstration that genomes can fold into highly specialized cell-type-specific scaffolds that enable megabase-scale regulatory associations.


Asunto(s)
Cromosomas de Insectos , Drosophila , Animales , Cromatina/genética , Empaquetamiento del ADN , Drosophila/genética , Mamíferos/genética , Neurogénesis , Neuronas , Factores de Transcripción , Proteínas de Drosophila , Genoma de los Insectos , Regulación de la Expresión Génica
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