TY - JOUR
T1 - A barcode screen for epigenetic regulators reveals a role for the NuB4/HAT-B histone acetyltransferase complex in histone turnover
AU - Verzijlbergen, Kitty F.
AU - van Welsem, Tibor
AU - Sie, Daoud
AU - Lenstra, Tineke L.
AU - Turner, Daniel J.
AU - Holstege, Frank C.P.
AU - Kerkhoven, Ron M.
AU - van Leeuwen, Fred
PY - 2011/10
Y1 - 2011/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=80055074120&partnerID=8YFLogxK
U2 - 10.1371/journal.pgen.1002284
DO - 10.1371/journal.pgen.1002284
M3 - Article
C2 - 21998594
AN - SCOPUS:80055074120
SN - 1553-7390
VL - 7
JO - PLoS Genetics
JF - PLoS Genetics
IS - 10
M1 - e1002284
ER -