Nucleome Dynamics during Retinal Development

视网膜发育过程中的核组动态变化

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作者:Jackie L Norrie,Marybeth S Lupo,Beisi Xu,Issam Al Diri,Marc Valentine,Daniel Putnam,Lyra Griffiths,Jiakun Zhang,Dianna Johnson,John Easton,Ying Shao,Victoria Honnell,Sharon Frase,Shondra Miller,Valerie Stewart,Xin Zhou,Xiang Chen,Michael A Dyer

Abstract

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.

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