Histone Chaperones Nap1 and Vps75 Regulate Histone Acetylation during Transcription Elongation

Xue, Yun-Shan; Kowalska, A.; Grabowska, Kamila; Przybyt, Katarzyna; Cichewicz, Magda A.; Rosario, Brian C. Del; Pemberton, Lucy F.

doi:10.1128/mcb.01121-12

Cited by 20 publications

(23 citation statements)

References 58 publications

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“…The active exchange of H2A-H2B could lead to the destabilization of the H3-H4 tetramer; thereby, Nap1 could also contribute to nucleosome disassembly. This is consistent with the findings that deletion of NAP1 reverses the cryptic transcript phenotype (interpreted as the by-product of underassembled chromatin) observed in mutant strains defective for other chromatin regulators (77) and that Nap1 has an important function in the eviction of histones during transcription in a mammalian in vitro system (17). Importantly, these varied functions of Nap1 are not redundant with other histone chaperones in vivo.…”

Section: Discussionsupporting

confidence: 78%

Histone Chaperone Nap1 Is a Major Regulator of Histone H2A-H2B Dynamics at the Inducible GAL Locus

Chen

D’Arcy

Radebaugh

et al. 2016

Molecular and Cellular Biology

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c Histone chaperones, like nucleosome assembly protein 1 (Nap1), play a critical role in the maintenance of chromatin architecture. Here, we use the GAL locus in Saccharomyces cerevisiae to investigate the influence of Nap1 on chromatin structure and histone dynamics during distinct transcriptional states. When the GAL locus is not expressed, cells lacking Nap1 show an accumulation of histone H2A-H2B but not histone H3-H4 at this locus. Excess H2A-H2B interacts with the linker DNA between nucleosomes, and the interaction is independent of the inherent DNA-binding affinity of H2A-H2B for these particular sequences as measured in vitro. When the GAL locus is transcribed, excess H2A-H2B is reversed, and levels of all chromatinbound histones are depleted in cells lacking Nap1. We developed an in vivo system to measure histone exchange at the GAL locus and observed considerable variability in the rate of exchange across the locus in wild-type cells. We recapitulate this variability with in vitro nucleosome reconstitutions, which suggests a contribution of DNA sequence to histone dynamics. We also find that Nap1 is required for transcription-dependent H2A-H2B exchange. Altogether, these results indicate that Nap1 is essential for maintaining proper chromatin composition and modulating the exchange of H2A-H2B in vivo.T he basic unit of chromatin is the nucleosome, which forms when DNA is wrapped around two copies each of the four core histones arranged as two histone H2A-H2B dimers and a histone H3-H4 tetramer (1). Nucleosomes are highly dynamic, capable of multiple structural transitions between completely assembled and entirely disassembled structures (2). Indeed, H2A-H2B and H3-H4 are actively exchanged during both DNA replication-dependent and -independent events (3-9). Chromatin transitions have the potential to profoundly affect gene expression, and a diverse spectrum of factors, including histone chaperones, participate in this process (10).Histone chaperones are histone-binding proteins that facilitate nucleosome assembly and/or disassembly in an ATP-independent fashion (11-13). The histone chaperone nucleosome assembly protein 1 (Nap1) is a highly conserved chaperone that binds H2A-H2B in vitro with nanomolar affinity (12, 14) in a conformation that shields interfaces required for nucleosome assembly (15). Although functional in the assembly of nucleosomes in vitro (16), a number of studies support a role for Nap1 in transcription-dependent processes of disassembly of nucleosomes. Nap1 is critical for the eviction of histones during transcription in a mammalian in vitro system (17), and Nap1 (with the ATP-dependent chromatin remodeler RSC [remodels the structure of chromatin]) can facilitate the elongation of RNA polymerase II (RNAPII) on chromatin templates using yeast in vitro systems (18,19). Our previous in vivo studies indicated that Nap1 prevents excess H2A-H2B accumulation on chromatin (20), and here, we expand our analysis to investigate the role of Nap1 in histone exchange and occupancy. As a model sy...

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Section: Discussionsupporting

confidence: 78%

Histone Chaperone Nap1 Is a Major Regulator of Histone H2A-H2B Dynamics at the Inducible GAL Locus

Chen

D’Arcy

Radebaugh

et al. 2016

Molecular and Cellular Biology

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“…We examined the ability of Nap1 expressed from a vector to rescue a Nap1-deletion strain grown in the presence of 6-azauracil (6-AU). 6-AU is widely used to identify proteins involved in transcription elongation, and a role for Nap1 in transcription has recently been reported (Hampsey, 1997; Xue et al, 2013). For the Nap1-deletion strain, rescue manifests as increased sensitivity to 6-AU when compared to a vector only control (Figure 4D).…”

Section: Resultsmentioning

confidence: 99%

Chaperone Nap1 Shields Histone Surfaces Used in a Nucleosome and Can Put H2A-H2B in an Unconventional Tetrameric Form

et al. 2013

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Summary The histone H2A-H2B heterodimer is an integral component of the nucleosome. The cellular localization and deposition of H2A-H2B into chromatin is regulated by numerous factors including histone chaperones such as Nucleosome Assembly Protein 1 (Nap1). We use hydrogen-deuterium exchange coupled to mass spectrometry to characterize H2A-H2B and Nap1. Unexpectedly, we find that at low ionic strength the α-helices in H2A-H2B are frequently sampling partially disordered conformations, and that binding to Nap1 reduces this conformational sampling. We identify the interaction surface between H2A-H2B and Nap1, and confirm its relevance both in vitro and in vivo. We show that two copies of H2A-H2B bound to a Nap1 homodimer form a tetramer with contacts between H2B chains similar to those in the four-helix bundle structural motif. The organization of the complex reveals that Nap1 competes with histone-DNA and inter-histone interactions observed in the nucleosome, thereby regulating the availability of histones for chromatin assembly.

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“…The loss of either chaperone leads to the depletion of histones in transcribed regions 187–189 . The re-establishment of chromatin structure after the passage of RNA polymerase II prevents the initiation of transcription from cryptic promoters 190,191 , and a substantial number of histone chaperones, including SPT2, SPT6, Rtt106, FACT, Vps75, Asf1 and HIRA 2,185,192 , are implicated in this process (reviewed in REF. 2) (FIG.…”

Section: Chaperones In Histone Deposition and Recyclingmentioning

confidence: 99%

Histone chaperone networks shaping chromatin function

Hammond

Strømme

Huang

et al. 2017

Nat Rev Mol Cell Biol

439

419

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The association of histones with specific chaperone complexes is important for their folding, oligomerization, post-translational modification, nuclear import, stability, assembly and genomic localization. In this way, the chaperoning of soluble histones is a key determinant of histone availability and fate, which affects all chromosomal processes, including gene expression, chromosome segregation and genome replication and repair. Here, we review the distinct structural and functional properties of the expanding network of histone chaperones. We emphasize how chaperones cooperate in the histone chaperone network and via co-chaperone complexes to match histone supply with demand, thereby promoting proper nucleosome assembly and maintaining epigenetic information by recycling modified histones evicted from chromatin.

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Histone Chaperones Nap1 and Vps75 Regulate Histone Acetylation during Transcription Elongation

Cited by 20 publications

References 58 publications

Histone Chaperone Nap1 Is a Major Regulator of Histone H2A-H2B Dynamics at the Inducible GAL Locus

Histone Chaperone Nap1 Is a Major Regulator of Histone H2A-H2B Dynamics at the Inducible GAL Locus

Chaperone Nap1 Shields Histone Surfaces Used in a Nucleosome and Can Put H2A-H2B in an Unconventional Tetrameric Form

Histone chaperone networks shaping chromatin function

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