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A Barcode Screen for Epigenetic Regulators Reveals a Role for the NuB4/HAT-B Histone Acetyltransferase Complex in Histone Turnover 1. 1. 2,3 4 5¤ Kitty F. Verzijlbergen , Tibor van Welsem , Daoud Sie , Tineke L. Lenstra , Daniel J. Turner , 4 2,3 1 Frank C. P. Holstege , Ron M. Kerkhoven , Fred van Leeuwen * 1 Department of Gene Regulation, Netherlands Cancer Institute, Amsterdam, The Netherlands, 2 Genome Center, Netherlands Cancer Institute, Amsterdam, The Netherlands, 3 Netherlands Proteomics Center, Amsterdam, The Netherlands, 4 Department of Molecular Cancer Research, University Medical Center Utrecht, Utrecht, The Netherlands, 5 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom Abstract Dynamic modification of histone proteins plays a key role in regulating gene expression. However, histones themselves can also be dynamic, which potentially affects the stability of histone modifications. To determine the molecular mechanisms of histone turnover, we developed a parallel screening method for epigenetic regulators by analyzing chromatin states on DNA barcodes. Histone turnover was quantified by employing a genetic pulse-chase technique called RITE, which was combined with chromatin immunoprecipitation and high-throughput sequencing. In this screen, the NuB4/HAT-B complex, containing the conserved type B histone acetyltransferase Hat1, was found to promote histone turnover. Unexpectedly, the three members of this complex could be functionally separated from each other as well as from the known interacting fact