title: A barcode screen for epigenetic regulators reveals a role for the NuB4/HAT-B histone acetyltransferase complex in histone turnover.
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.
authors: Department of Gene Regulation, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors: Kitty F
authors: KF
authors: Verzijlbergen
authors: Tibor
authors: T
authors: van Welsem
authors: Daoud
authors: D
authors: Sie
authors: Tineke L
authors: TL
authors: Lenstra
authors: Daniel J
authors: DJ
authors: Turner
authors: Frank C P
authors: FC
authors: Holstege
authors: Ron M
authors: RM
authors: Kerkhoven
authors: Fred
authors: F
authors: van Leeuwen
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D058893:DNA Barcoding, Taxonomic; D044127:Epigenesis, Genetic / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D049790:Nuclear Export Signals / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C109731:ASF1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D002843:Chromatin; D006657:Histones; D018832:Molecular Chaperones; D049790:Nuclear Export Signals; D029701:Saccharomyces cerevisiae Proteins; D051548:Histone Acetyltransferases; C110880:histone acetyltransferase type B complex