scholarly journals Two factor authentication: Asf1 mediates crosstalk between H3 K14 and K56 acetylation

2019 ◽  
Vol 47 (14) ◽  
pp. 7380-7391 ◽  
Author(s):  
Joy M Cote ◽  
Yin-Ming Kuo ◽  
Ryan A Henry ◽  
Hataichanok Scherman ◽  
Daniel D Krzizike ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Repair ◽  
Histone Acetylation ◽  
Histone H3 ◽  
Histone Chaperone ◽  
Biochemical Data ◽  
Genome Replication ◽  
Histone Chaperones ◽  
Post Translational Modifications ◽  
Lysine Acetyltransferase

Abstract The ability of histone chaperone Anti-silencing factor 1 (Asf1) to direct acetylation of lysine 56 of histone H3 (H3K56ac) represents an important regulatory step in genome replication and DNA repair. In Saccharomyces cerevisiae, Asf1 interacts functionally with a second chaperone, Vps75, and the lysine acetyltransferase (KAT) Rtt109. Both Asf1 and Vps75 can increase the specificity of histone acetylation by Rtt109, but neither alter selectivity. However, changes in acetylation selectivity have been observed in histones extracted from cells, which contain a plethora of post-translational modifications. In the present study, we use a series of singly acetylated histones to test the hypothesis that histone pre-acetylation and histone chaperones function together to drive preferential acetylation of H3K56. We show that pre-acetylated H3K14ac/H4 functions with Asf1 to drive specific acetylation of H3K56 by Rtt109–Vps75. Additionally, we identified an exosite containing an acidic patch in Asf1 and show that mutations to this region alter Asf1-mediated crosstalk that changes Rtt109–Vps75 selectivity. Our proposed mechanism suggests that Gcn5 acetylates H3K14, recruiting remodeler complexes, allowing for the Asf1-H3K14ac/H4 complex to be acetylated at H3K56 by Rtt109–Vps75. This mechanism explains the conflicting biochemical data and the genetic links between Rtt109, Vps75, Gcn5 and Asf1 in the acetylation of H3K56.

scholarly journals Histone transfer among chaperones

2012 ◽  
Vol 40 (2) ◽  
pp. 357-363 ◽  
Author(s):  
Wallace H. Liu ◽  
Mair E.A. Churchill
Keyword(s):  
Histone H3 ◽  
Histone Chaperone ◽  
Chromatin Assembly ◽  
Histone Chaperones ◽  
Nucleosome Assembly ◽  
Post Translational Modifications ◽  
Chromatin Dynamics ◽  
Nucleosomal Dna ◽  
Chaperone Interactions ◽  
Dependent Processes

The eukaryotic processes of nucleosome assembly and disassembly govern chromatin dynamics, in which histones exchange in a highly regulated manner to promote genome accessibility for all DNA-dependent processes. This regulation is partly carried out by histone chaperones, which serve multifaceted roles in co-ordinating the interactions of histone proteins with modification enzymes, nucleosome remodellers, other histone chaperones and nucleosomal DNA. The molecular details of the processes by which histone chaperones promote delivery of histones among their many functional partners are still largely undefined, but promise to offer insights into epigenome maintenance. In the present paper, we review recent findings on the histone chaperone interactions that guide the assembly of histones H3 and H4 into chromatin. This evidence supports the concepts of histone post-translational modifications and specific histone chaperone interactions as guiding principles for histone H3/H4 transactions during chromatin assembly.

scholarly journals Histone chaperone FACT represses retrotransposon MERVL and MERVL-derived cryptic promoters

2020 ◽  
Vol 48 (18) ◽  
pp. 10211-10225 ◽  
Author(s):  
Fuquan Chen ◽  
Weiyu Zhang ◽  
Dan Xie ◽  
Tingting Gao ◽  
Zhiqiang Dong ◽  
...  
Keyword(s):  
Target Genes ◽  
Critical Role ◽  
Histone H3 ◽  
Embryonic Stem ◽  
Histone Chaperone ◽  
Endogenous Retroviruses ◽  
Histone Chaperones ◽  
Cryptic Transcription ◽  
Unique Mechanism ◽  
Cryptic Promoters

Abstract Endogenous retroviruses (ERVs) were usually silenced by various histone modifications on histone H3 variants and respective histone chaperones in embryonic stem cells (ESCs). However, it is still unknown whether chaperones of other histones could repress ERVs. Here, we show that H2A/H2B histone chaperone FACT plays a critical role in silencing ERVs and ERV-derived cryptic promoters in ESCs. Loss of FACT component Ssrp1 activated MERVL whereas the re-introduction of Ssrp1 rescued the phenotype. Additionally, Ssrp1 interacted with MERVL and suppressed cryptic transcription of MERVL-fused genes. Remarkably, Ssrp1 interacted with and recruited H2B deubiquitinase Usp7 to Ssrp1 target genes. Suppression of Usp7 caused similar phenotypes as loss of Ssrp1. Furthermore, Usp7 acted by deubiquitinating H2Bub and thereby repressed the expression of MERVL-fused genes. Taken together, our study uncovers a unique mechanism by which FACT complex silences ERVs and ERV-derived cryptic promoters in ESCs.

UV sensitive mutations in histone H3 in Saccharomyces cerevisiae that alter specific K79 methylation states genetically act through distinct DNA repair pathways

2008 ◽  
Vol 53 (5) ◽  
pp. 259-274 ◽  
Author(s):  
Margery L. Evans ◽  
Lindsey J. Bostelman ◽  
Ashley M. Albrecht ◽  
Andrew M. Keller ◽  
Natasha T. Strande ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Repair ◽  
Histone H3 ◽  
Repair Pathways

scholarly journals Asf1 Can Promote Trimethylation of H3 K36 by Set2

2010 ◽  
Vol 30 (5) ◽  
pp. 1116-1129 ◽  
Author(s):  
Ling-ju Lin ◽  
Laura V. Minard ◽  
Gerald C. Johnston ◽  
Richard A. Singer ◽  
Michael C. Schultz
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Rna Polymerase ◽  
Histone Acetylation ◽  
Rna Polymerase Ii ◽  
Posttranslational Modification ◽  
Protein Complexes ◽  
Histone H3 ◽  
Cross Linking ◽  
Coding Region ◽  
Repressive Chromatin

ABSTRACT Asf1 is a conserved histone H3/H4 chaperone that can assemble and disassemble nucleosomes and promote histone acetylation. Set2 is an H3 K36 methyltransferase. The functions of these proteins intersect in the context of transcription elongation by RNA polymerase II: both contribute to the establishment of repressive chromatin structures that inhibit spurious intragenic transcription. Here we characterize further interactions between budding yeast (Saccharomyces cerevisiae) Asf1 and Set2 using assays of intragenic transcription, H3/H4 posttranslational modification, coding region cross-linking of Asf1 and Set2, and cooccurrence of Asf1 and Set2 in protein complexes. We find that at some genes Asf1 and Set2 control chromatin metabolism as components of separate pathways. However, the existence of a low-abundance complex containing both proteins suggests that Asf1 and Set2 can more directly collaborate in chromatin regulation. Consistent with this possibility, we show that Asf1 stimulates Set2 occupancy of the coding region of a highly transcribed gene by a mechanism that depends on Asf1 binding to H3/H4. This function of Asf1 promotes the switch from di- to trimethylation of H3 K36 at that gene. These results support the view that Set2 function in chromatin metabolism can intimately involve histone chaperone Asf1.

scholarly journals Eaf3 Regulates the Global Pattern of Histone Acetylation in Saccharomyces cerevisiae

2004 ◽  
Vol 24 (2) ◽  
pp. 757-764 ◽  
Author(s):  
Juliet L. Reid ◽  
Zarmik Moqtaderi ◽  
Kevin Struhl
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Histone Acetylation ◽  
Transcriptional Profiling ◽  
Histone H3 ◽  
Small Subset ◽  
Genomic Profile ◽  
Promoter Regions ◽  
Global Pattern ◽  
Coding Sequences ◽  
Negative Effect

ABSTRACT Saccharomyces cerevisiae has a global pattern of histone acetylation in which histone H3 and H4 acetylation levels are lower at protein-coding sequences than at promoter regions. The loss of Eaf3, a subunit of the NuA4 histone acetylase and Rpd3 histone deacetylase complexes, greatly alters the genomic profile of histone acetylation, with the effects on H4 appearing to be more pronounced than those on H3. Specifically, the loss of Eaf3 causes increases in H3 and H4 acetylation at coding sequences and decreases at promoters, such that histone acetylation levels become evenly distributed across the genome. Eaf3 does not affect the overall level of H4 acetylation, the recruitment of the NuA4 catalytic subunit Esa1 to target promoters, or the level of transcription of the genes analyzed for histone acetylation. Whole-genome transcriptional profiling indicates that Eaf3 plays a positive, but quantitatively modest, role in the transcription of a small subset of genes, whereas it has a negative effect on very few genes. We suggest that Eaf3 regulates the genomic profile of histone H3 and H4 acetylation in a manner that does not involve targeted recruitment and is independent of transcriptional activity.

scholarly journals Coordinated Action of Nap1 and RSC in Disassembly of Tandem Nucleosomes

2016 ◽  
Vol 36 (17) ◽  
pp. 2262-2271 ◽  
Author(s):  
Rashmi Prasad ◽  
Sheena D'Arcy ◽  
Arjan Hada ◽  
Karolin Luger ◽  
Blaine Bartholomew
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Mutational Analysis ◽  
Histone Chaperone ◽  
Histone Chaperones ◽  
Content Type ◽  
Chromatin Remodelers ◽  
Coordinated Action

The SWI/SNF and RSC family of ATP-dependent chromatin remodelers disassembles nucleosomes by moving nucleosomes into the vicinity of adjoining nucleosomes. We found that the histone chaperone Nap1 efficiently promotes disassembly of adjacent nucleosomes with which RSC collides and not the disassembly of nucleosomes mobilized by RSC. Nap1 is specific to RSC, as it does not target SWI/SNF, its paralog inSaccharomyces cerevisiae. Extensive mutational analysis of Nap1 has revealed that Nap1 affinity for histones H2A-H2B and H3-H4 and its ability to displace histones from DNA are required for Nap1 to enhance RSC-mediated disassembly. Other histone chaperones, such as Vps75, that also bind histones are not able to enhance RSC-mediated disassembly. Our study suggests a mechanism by which Nap1 is recruited to actively transcribed regions and assists in the passage of the transcription complex through chromatin, and it provides a novel mechanism for the coordinated action of RSC and Nap1.

scholarly journals Chaperone Control of the Activity and Specificity of the Histone H3 Acetyltransferase Rtt109

2008 ◽  
Vol 28 (13) ◽  
pp. 4342-4353 ◽  
Author(s):  
Jeffrey Fillingham ◽  
Judith Recht ◽  
Andrea C. Silva ◽  
Bernhard Suter ◽  
Andrew Emili ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Histone Acetyltransferase ◽  
Histone H3 ◽  
Histone Chaperone ◽  
Genetic Interactions ◽  
Whole Genome ◽  
Genome Screen ◽  
Associated Lesions

ABSTRACT Acetylation of Saccharomyces cerevisiae histone H3 on K56 by the histone acetyltransferase (HAT) Rtt109 is important for repairing replication-associated lesions. Rtt109 purifies from yeast in complex with the histone chaperone Vps75, which stabilizes the HAT in vivo. A whole-genome screen to identify genes whose deletions have synthetic genetic interactions with rtt109Δ suggests Rtt109 has functions in addition to DNA repair. We show that in addition to its known H3-K56 acetylation activity, Rtt109 is also an H3-K9 HAT, and we show that Rtt109 and Gcn5 are the only H3-K9 HATs in vivo. Rtt109's H3-K9 acetylation activity in vitro is enhanced strongly by Vps75. Another histone chaperone, Asf1, and Vps75 are both required for acetylation of lysine 9 on H3 (H3-K9ac) in vivo by Rtt109, whereas H3-K56ac in vivo requires only Asf1. Asf1 also physically interacts with the nuclear Hat1/Hat2/Hif1 complex that acetylates H4-K5 and H4-K12. We suggest Asf1 is capable of assembling into chromatin H3-H4 dimers diacetylated on both H4-K5/12 and H3-K9/56.

scholarly journals The Histone Chaperone Asf1p Mediates Global Chromatin Disassemblyin Vivo

2004 ◽  
Vol 279 (50) ◽  
pp. 52069-52074 ◽  
Author(s):  
Melissa W. Adkins ◽  
Jessica K. Tyler
Keyword(s):  
Histone Acetylation ◽  
Chromatin Structure ◽  
Histone H3 ◽  
Dnase I ◽  
Chromatin Assembly ◽  
Eukaryotic Genome ◽  
Micrococcal Nuclease ◽  
Histone Chaperones ◽  
Assembly Factor

The packaging of the eukaryotic genome into chromatin is likely to be mediated by chromatin assembly factors, including histone chaperones. We investigated the function of the histone H3/H4 chaperones anti-silencing function 1 (Asf1p) and chromatin assembly factor 1 (CAF-1)in vivo. Analysis of chromatin structure by accessibility to micrococcal nuclease and DNase I digestion demonstrated that the chromatin from CAF-1 mutant yeast has increased accessibility to these enzymes. In agreement, the supercoiling of the endogenous 2μ plasmid is reduced in yeast lacking CAF-1. These results indicate that CAF-1 mutant yeast globally under-assemble their genome into chromatin, consistent with a role for CAF-1 in chromatin assemblyin vivo. By contrast,asf1mutants globally over-assemble their genome into chromatin, as suggested by decreased accessibility of their chromatin to micrococcal nuclease and DNase I digestion and increased supercoiling of the endogenous 2μ plasmid. Deletion ofASF1causes a striking loss of acetylation on histone H3 lysine 9, but this is not responsible for the altered chromatin structure inasf1mutants. These data indicate that Asf1p may have a global role in chromatin disassembly and an unexpected role in histone acetylationin vivo.

scholarly journals NASP maintains histone H3–H4 homeostasis through two distinct H3 binding modes

2021 ◽  
Author(s):  
Hongyu Bao ◽  
Massimo Carraro ◽  
Valentin Flury ◽  
Yanhong Liu ◽  
Min Luo ◽  
...  
Keyword(s):  
Histone H3 ◽  
Histone Chaperone ◽  
Histone Chaperones ◽  
Binding Modes ◽  
Histone Binding ◽  
Chaperone Complex

Histone chaperones regulate all aspects of histone metabolism. NASP is a major histone chaperone for H3–H4 dimers critical for preventing histone degradation.Here, we identify two distinct histone binding modes of NASP and reveal how they cooperate to ensure histone H3–H4 supply. We determine the structures of a sNASP dimer, a complex of sNASP with an H3 α3 peptide, and the sNASP–H3–H4–ASF1b co-chaperone complex.

scholarly journals Pre-acetylation in the presence of Asf1 alters Rtt019-Vps75 selectivity

2018 ◽  
Author(s):  
Joy M. Cote ◽  
Yin-Ming Kuo ◽  
Ryan A. Henry ◽  
Hataichanok Scherman ◽  
Andrew J. Andrews
Keyword(s):  
Critical Role ◽  
Eukaryotic Cell ◽  
Histone Chaperones ◽  
Post Translational Modifications ◽  
Damage Repair ◽  
Acetylation Site ◽  
Site Selectivity ◽  
Lysine Acetyltransferase ◽  
The Impact ◽  
Enzyme Selectivity

ABSTRACTAcetylation of histones plays a critical role in maintaining the epigenetic state of the eukaryotic cell. One such acetylation site critical for DNA damage repair is H3K56ac. In Saccharomyces cerevisiae, H3K56ac is thought to be driven mainly by Rtt109, a lysine acetyltransferase (KAT) that associates with the histone chaperones Vps75 and Asf1. Both of these chaperones can increase the specificity of histone acetylation by Rtt109, but neither alter the selectivity. It has been shown that histones extracted from cells (Drosophila), presumably containing pre-acetylated histones, can incorporate higher amounts of H3K56ac relative to recombinant non-acetylated histones. We hypothesized that histone pre-acetylation and histone chaperones could function together to drive acetylation of H3K56. In the present study, we test this hypothesis using a series of singly acetylated histones to determine the impact of crosstalk on enzyme selectivity. Our data suggest that crosstalk between acetylation sites plays a major role in altering the selectivity of Rtt109-Vps75 and that the histone chaperone Asf1 mediates this crosstalk. Specifically, we show that H3K14ac/H4 functions with Asf1 to drive H3K56ac by Rtt109-Vps75. We identified an acidic patch in Asf1 that mediates this cross-talk and show that mutations to this region can alter the Asf1 mediated crosstalk that changes Rtt109-Vps75 selectivity. These data explain the genetic link between Gcn5, which acetylates H3K14 and Rtt109. More broadly these data demonstrate that acetylation sites can dictate site selectivity even in the absence of a bromodomain and helps to explain the limited complexity that has been observed of the histone post-translational modifications patterns by global proteomic studies.

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