The Replication-independent Histone H3-H4 Chaperones HIR, ASF1, and RTT106 Co-operate to Maintain Promoter Fidelity

Silva, Andréa C.; Xu, Xiaomeng; Kim, Hyun Soo; Fillingham, Jeffrey; Kislinger, Thomas; Mennella, Thomas A.; Keogh, Michael‐Christopher

doi:10.1074/jbc.m111.316489

Cited by 56 publications

(72 citation statements)

References 63 publications

(92 reference statements)

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“…Notably, the deletion of RTT109 or ASF1, which prevents H3K56 acetylation and consequently decreases Rtt106:H3 binding, reduces Rtt106 enrichment at histone promoters ( Fig. 1A and B) (32,33,51) without reducing HIR localization (Fig. 1C) (16).…”

Section: Rtt106:h3 Binding Was Required For Histone Gene Repressionmentioning

confidence: 99%

“…Mutations that disrupt Rtt106:H3 binding lead to reduced Rtt106 enrichment at histone gene promoters (32,51), suggesting that the Rtt106:HIR interaction might be mediated by histone proteins. Asf1 copurifies with the HIR complex (21), and in asf1⌬ cells, Rtt106 localization is reduced, leading to inappropriate histone expression outside S phase (51,53). Although these data suggest that Asf1 plays a direct role in histone gene regulation, whether Asf1 localizes to histone gene promoters as a member of the HIR:Rtt106 regulatory complex was unclear.…”

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confidence: 99%

“…Rtt106 is recruited to histone gene regulatory regions in a HIR-dependent manner (16), and it contributes to transcriptional repression through the direct recruitment of the RSC chromatinremodeling complex outside S phase (15,42). Mutations that disrupt Rtt106:H3 binding lead to reduced Rtt106 enrichment at histone gene promoters (32,51), suggesting that the Rtt106:HIR interaction might be mediated by histone proteins. Asf1 copurifies with the HIR complex (21), and in asf1⌬ cells, Rtt106 localization is reduced, leading to inappropriate histone expression outside S phase (51,53).…”

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confidence: 99%

“…Additionally, CAF-1 performs an overlapping function with Asf1, Rtt106, and the HIR complex to maintain silent chromatin (25,26,30,49,56). The involvement of histone chaperones in both the assembly of histone proteins into chromatin and the regulation of histone gene transcription suggests that the two processes might be linked (13,51). Thus, histone chaperones might facilitate a negative-feedback loop to allow cells to adjust histone gene transcription as a function of free histone protein levels.…”

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confidence: 99%

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Direct Interplay among Histones, Histone Chaperones, and a Chromatin Boundary Protein in the Control of Histone Gene Expression

Zunder

Rine

2012

Molecular and Cellular Biology

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In Saccharomyces cerevisiae, the histone chaperone Rtt106 binds newly synthesized histone proteins and mediates their delivery into chromatin during transcription, replication, and silencing. Rtt106 is also recruited to histone gene regulatory regions by the HIR histone chaperone complex to ensure S-phase-specific expression. Here we showed that this Rtt106:HIR complex included Asf1 and histone proteins. Mutations in Rtt106 that reduced histone binding reduced Rtt106 enrichment at histone genes, leading to their increased transcription. Deletion of the chromatin boundary element Yta7 led to increased Rtt106:H3 binding, increased Rtt106 enrichment at histone gene regulatory regions, and decreased histone gene transcription at the HTA1-HTB1 locus. These results suggested a unique regulatory mechanism in which Rtt106 sensed the level of histone proteins to maintain the proper level of histone gene transcription. The role of these histone chaperones and Yta7 differed markedly among the histone gene loci, including the two H3-H4 histone gene pairs. Defects in silencing in rtt106 mutants could be partially accounted for by Rtt106-mediated changes in histone gene repression. These studies suggested that feedback mediated by histone chaperone complexes plays a pivotal role in regulating histone gene transcription. Cell cycle-regulated transcription of the canonical histone genes is a hallmark of eukaryotic organisms. During S phase, a coordinated burst of histone gene transcription is required to double the level of histone proteins to package newly replicated DNA into chromatin (13,22). The tight coupling of both the timing and the level of histone gene expression with DNA synthesis is critical for cell viability. Mutations that perturb DNA replication lead to altered histone gene transcription (3, 23). Conversely, misregulation of the timing and/or level of histone gene expression leads to genomic instability and cell cycle defects (23,43). Consequently, cells have evolved a complex regulatory mechanism to repress histone gene transcription outside S phase and to promote a precise level of transcription during S phase.The Saccharomyces cerevisiae genome contains two nonallelic copies of each canonical histone gene which are organized in head-to-head pairs of H2A-H2B (HTA1-HTB1 and HTA2-HTB2) and H3-H4 (HHT1-HHF1 and HHT2-HHF2). Nucleosomes, the fundamental units of chromatin structure, contain two H2A/H2B dimers, one H3/H4 tetramer, and ϳ147 bp of DNA wrapped around the outer surface (37). Repression of histone transcription outside S phase is maintained by the HIR H3/H4 histone-protein chaperone complex, referred to here as the HIR complex (Hir1, Hir2, Hir3, and Hpc2). The HIR complex localizes to negative (NEG) sequence elements within the regulatory regions of HTA1-HTB1, 45,59). Although HTA2-HTB2 transcription is S-phase specific, its promoter does not contain NEG elements, and the factors involved in its HIRindependent repression are unknown (45). A recent study implicated two additional H3/H4 chaperones, Rtt106 ...

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Section: Rtt106:h3 Binding Was Required For Histone Gene Repressionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Direct Interplay among Histones, Histone Chaperones, and a Chromatin Boundary Protein in the Control of Histone Gene Expression

Zunder

Rine

2012

Molecular and Cellular Biology

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“…In the complementary experiment we observed that the HIR2 deletion did not affect rrm3D viability ( Figure S1). Given that HIR2 is required for the integrity of the HIR complex and, consequently, for histone deposition activity of Asf1/HIR (Green et al 2005;Silva et al 2012), these observations demonstrate that the replicationindependent chromatin assembly function of Asf1 is not required for rrm3D cell viability. We next evaluated the contribution of the single-residue substitution V94R, important for histone H3 interaction (Mousson et al 2005;Jiao et al 2012).…”

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Replisome Function During Replicative Stress Is Modulated by Histone H3 Lysine 56 Acetylation Through Ctf4

et al. 2015

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Histone H3 lysine 56 acetylation in Saccharomyces cerevisiae is required for the maintenance of genome stability under normal conditions and upon DNA replication stress. Here we show that in the absence of H3 lysine 56 acetylation replisome components become deleterious when replication forks collapse at natural replication block sites. This lethality is not a direct consequence of chromatin assembly defects during replication fork progression. Rather, our genetic analyses suggest that in the presence of replicative stress H3 lysine 56 acetylation uncouples the Cdc45-Mcm2-7-GINS DNA helicase complex and DNA polymerases through the replisome component Ctf4. In addition, we discovered that the N-terminal domain of Ctf4, necessary for the interaction of Ctf4 with Mms22, an adaptor protein of the Rtt101-Mms1 E3 ubiquitin ligase, is required for the function of the H3 lysine 56 acetylation pathway, suggesting that replicative stress promotes the interaction between Ctf4 and Mms22. Taken together, our results indicate that Ctf4 is an essential member of the H3 lysine 56 acetylation pathway and provide novel mechanistic insights into understanding the role of H3 lysine 56 acetylation in maintaining genome stability upon replication stress. KEYWORDS Ctf4; H3K56 acetylation; Mms22; replicative stress; replisome T HE eukaryotic replisome consists of polymerases and an essential DNA helicase that are linked by a number of factors assembled during the initiation of chromosome replication. Progression of the replication fork depends on the activity of the replisome progression complex (RPC). This complex is uniquely present during S phase (Gambus et al. 2006) and remains associated with the replication fork until completion of DNA replication. In Saccharomyces cerevisiae, the RPC is made up of Mcm10, Mrc1, Tof1, Csm3, Ctf4, Top1, FACT (Spt16 and Pob3), and the CMG complex comprising Cdc45, , and the go ichi ni san (GINS) complex. The CMG constitutes the core replicative helicase responsible for the movement and activities of the replication fork (Pacek et al. 2006;Bochman and Schwacha 2009).The link between helicase and polymerases is a crucial determinant for the regulation of the replisome. The leadingstrand DNA polymerase-ɛ was recently shown to be integrated into the replisome via an interaction with the GINS complex (Sengupta et al. 2013). Furthermore, the DNA polymerasea-primase complex, which initiates DNA synthesis at replication origins and continues to prime Okazaki fragments at the fork, remains associated with the RPC via the Ctf4 trimer, which simultaneously interacts with the GINS complex (Gambus et al. 2009;Tanaka et al. 2009;Gosnell and Christensen 2011;Simon et al. 2014).Cells have evolved different mechanisms to maintain genome integrity under the conditions threatening replication progression (Jossen and Bermejo 2013;Leman and Noguchi 2013). The S-phase checkpoint mediated by MRC1 was initially characterized as a pathway activated by fork stalling and able to both stabilize the replisome and dela...

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Set2 mediated H3 lysine 36 methylation: regulation of transcription elongation and implications in organismal development

Venkatesh

Workman

2013

WIREs Developmental Biology

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Set2 is a RNA Polymerase II (RNAPII) associated histone methyltransferase involved in the co-transcriptional methylation of the H3 K36 residue (H3K36me). It is responsible for multiple degrees of methylation (mono-, di-, tri-), each of which has a distinct functional consequence. The extent of methylation and its genomic distribution is determined by different factors that co-ordinate to achieve a functional outcome. In yeast, the Set2-mediated H3K36me is involved in suppressing histone exchange, preventing hyperacetylation and promoting maintenance of well-spaced chromatin structure over the coding regions. In metazoans, separation of this enzymatic activity affords greater functional diversity extending beyond the control of transcription elongation to developmental gene regulation. This review focuses on the molecular aspects of the Set2 distribution and function, and discusses the role played by H3 K36 methyl mark in organismal development.

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The Replication-independent Histone H3-H4 Chaperones HIR, ASF1, and RTT106 Co-operate to Maintain Promoter Fidelity

Cited by 56 publications

References 63 publications

Direct Interplay among Histones, Histone Chaperones, and a Chromatin Boundary Protein in the Control of Histone Gene Expression

Direct Interplay among Histones, Histone Chaperones, and a Chromatin Boundary Protein in the Control of Histone Gene Expression

Replisome Function During Replicative Stress Is Modulated by Histone H3 Lysine 56 Acetylation Through Ctf4

Set2 mediated H3 lysine 36 methylation: regulation of transcription elongation and implications in organismal development

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