A barcode screen for epigenetic regulators reveals a role for the NuB4/HAT-B histone acetyltransferase complex in histone turnover

Kitty F Verzijlbergen, Tibor van Welsem, Daoud Sie, Tineke L Lenstra, Daniel J Turner, Frank C P Holstege, Ron M Kerkhoven, Fred van Leeuwen

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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 factor and histone chaperone Asf1. Thus, systematic and direct interrogation of chromatin structure on DNA barcodes can lead to the discovery of genes and pathways involved in chromatin modification and dynamics.

Original languageEnglish
Pages (from-to)e1002284
JournalPLoS Genetics
Volume7
Issue number10
DOIs
Publication statusPublished - Oct 2011

Cite this

Verzijlbergen, K. F., van Welsem, T., Sie, D., Lenstra, T. L., Turner, D. J., Holstege, F. C. P., ... van Leeuwen, F. (2011). A barcode screen for epigenetic regulators reveals a role for the NuB4/HAT-B histone acetyltransferase complex in histone turnover. PLoS Genetics, 7(10), e1002284. https://doi.org/10.1371/journal.pgen.1002284