A Barcode Screen for Epigenetic Regulators Reveals a Role for the NuB4/HAT-B Histone Acetyltransferase Complex in Histone Turnover
Overview
Authors
Affiliations
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.
Pratx L, Wendering P, Kappel C, Nikoloski Z, Baurle I EMBO J. 2023; 42(24):e113595.
PMID: 37937667 PMC: 10711655. DOI: 10.15252/embj.2023113595.
The histone code of the fungal genus uncovered by evolutionary and proteomic analyses.
Zhang X, Noberini R, Bonaldi T, Collemare J, Seidl M Microb Genom. 2022; 8(9).
PMID: 36129736 PMC: 9676040. DOI: 10.1099/mgen.0.000856.
Rtt109 promotes nucleosome replacement ahead of the replication fork.
Jonas F, Yaakov G, Barkai N Genome Res. 2022; 32(6):1089-1098.
PMID: 35609993 PMC: 9248883. DOI: 10.1101/gr.276674.122.
Kollenstart L, van der Horst S, Vreeken K, Janssen G, Martino F, Vlaming H Sci Rep. 2021; 11(1):12795.
PMID: 34140538 PMC: 8211816. DOI: 10.1038/s41598-021-91359-0.
Application of Recombination -Induced Tag Exchange (RITE) to study histone dynamics in human cells.
Molenaar T, Pages-Gallego M, Meyn V, van Leeuwen F Epigenetics. 2020; 15(9):901-913.
PMID: 32228348 PMC: 7518693. DOI: 10.1080/15592294.2020.1741777.