Nucleome Dynamics during Retinal Development

视网膜发育过程中的核组动力学

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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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