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Cell. 2015 Aug 13;162(4):911-23. doi: 10.1016/j.cell.2015.07.035.

Identification of Gene Positioning Factors Using High-Throughput Imaging Mapping.

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National Cancer Institute, NIH, Bethesda, MD 20892, USA.
High Throughput Imaging Facility (HiTIF), National Cancer Institute, NIH, Bethesda, MD 20892, USA.
National Cancer Institute, NIH, Bethesda, MD 20892, USA. Electronic address:


Genomes are arranged non-randomly in the 3D space of the cell nucleus. Here, we have developed HIPMap, a high-precision, high-throughput, automated fluorescent in situ hybridization imaging pipeline, for mapping of the spatial location of genome regions at large scale. High-throughput imaging position mapping (HIPMap) enabled an unbiased siRNA screen for factors involved in genome organization in human cells. We identify 50 cellular factors required for proper positioning of a set of functionally diverse genomic loci. Positioning factors include chromatin remodelers, histone modifiers, and nuclear envelope and pore proteins. Components of the replication and post-replication chromatin re-assembly machinery are prominently represented among positioning factors, and timely progression of cells through replication, but not mitosis, is required for correct gene positioning. Our results establish a method for the large-scale mapping of genome locations and have led to the identification of a compendium of cellular factors involved in spatial genome organization.

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