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Neuron ; 104(3): 512-528.e11, 2019 11 06.
Artículo en Inglés | MEDLINE | ID: mdl-31493975

RESUMEN

More than 8,000 genes are turned on or off as progenitor cells produce the 7 classes of retinal cell types during development. Thousands of enhancers are also active in the developing retinae, many having features of cell- and developmental stage-specific activity. We studied dynamic changes in the 3D chromatin landscape important for precisely orchestrated changes in gene expression during retinal development by ultra-deep in situ Hi-C analysis on murine retinae. We identified developmental-stage-specific changes in chromatin compartments and enhancer-promoter interactions. We developed a machine learning-based algorithm to map euchromatin and heterochromatin domains genome-wide and overlaid it with chromatin compartments identified by Hi-C. Single-cell ATAC-seq and RNA-seq were integrated with our Hi-C and previous ChIP-seq data to identify cell- and developmental-stage-specific super-enhancers (SEs). We identified a bipolar neuron-specific core regulatory circuit SE upstream of Vsx2, whose deletion in mice led to the loss of bipolar neurons.


Asunto(s)
Eucromatina/metabolismo , Regulación del Desarrollo de la Expresión Génica/fisiología , Heterocromatina/metabolismo , Retina/embriología , Células Bipolares de la Retina/metabolismo , Animales , Cromatina/metabolismo , Secuenciación de Inmunoprecipitación de Cromatina , Elementos de Facilitación Genéticos , Redes Reguladoras de Genes , Proteínas de Homeodominio/genética , Aprendizaje Automático , Ratones , Lámina Nuclear/metabolismo , Regiones Promotoras Genéticas , RNA-Seq , Receptores Citoplasmáticos y Nucleares/genética , Retina/citología , Retina/metabolismo , Retina/ultraestructura , Células Bipolares de la Retina/citología , Células Fotorreceptoras Retinianas Bastones/citología , Células Fotorreceptoras Retinianas Bastones/metabolismo , Análisis de la Célula Individual , Factores de Transcripción/genética , Receptor de Lamina B
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