H3–H4 Histone Chaperone Pathways

Nucleosomes compact and organize genetic material on a structural level. However, they also alter local chromatin accessibility through changes in their position, through the incorporation of histone variants, and through a vast array of histone posttranslational modifications. The dynamic nature of chromatin requires histone chaperones to process, deposit, and evict histones in different tissues and at different times in the cell cycle. This review focuses on the molecular details of canonical and variant H3–H4 histone chaperone pathways that lead to histone deposition on DNA as they are currently understood. Emphasis is placed on the most established pathways beginning with the folding, posttranslational modification, and nuclear import of newly synthesized H3–H4 histones. Next, we review the deposition of replication-coupled H3.1–H4 in S-phase and replication-independent H3.3–H4 via alternative histone chaperone pathways. Highly specialized histone chaperones overseeing the deposition of histone variants are also briefly discussed.

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The Histone Chaperone HIRA Is a Positive Regulator of Seed Germination

International Journal of Molecular Sciences ◽

10.3390/ijms22084031 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4031

Author(s):

Elodie Layat ◽

Marie Bourcy ◽

Sylviane Cotterell ◽

Julia Zdzieszyńska ◽

Sophie Desset ◽

...

Keyword(s):

Seed Germination ◽

Seed Dormancy ◽

Elongation Factor ◽

Histone Variants ◽

Chromatin Accessibility ◽

Histone Chaperone ◽

Histone Chaperones ◽

Genes Encoding ◽

Controlled Deterioration ◽

Histone Deposition

Histone chaperones regulate the flow and dynamics of histone variants and ensure their assembly into nucleosomal structures, thereby contributing to the repertoire of histone variants in specialized cells or tissues. To date, not much is known on the distribution of histone variants and their modifications in the dry seed embryo. Here, we bring evidence that genes encoding the replacement histone variant H3.3 are expressed in Arabidopsis dry seeds and that embryo chromatin is characterized by a low H3.1/H3.3 ratio. Loss of HISTONE REGULATOR A (HIRA), a histone chaperone responsible for H3.3 deposition, reduces cellular H3 levels and increases chromatin accessibility in dry seeds. These molecular differences are accompanied by increased seed dormancy in hira-1 mutant seeds. The loss of HIRA negatively affects seed germination even in the absence of HISTONE MONOUBIQUITINATION 1 or TRANSCRIPTION ELONGATION FACTOR II S, known to be required for seed dormancy. Finally, hira-1 mutant seeds show lower germination efficiency when aged under controlled deterioration conditions or when facing unfavorable environmental conditions such as high salinity. Altogether, our results reveal a dependency of dry seed chromatin organization on the replication-independent histone deposition pathway and show that HIRA contributes to modulating seed dormancy and vigor.

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Histone chaperones exhibit conserved functionality in nucleosome remodeling

10.1101/2022.01.13.476140 ◽

2022 ◽

Author(s):

Pedro Buzon ◽

Alejandro Velazquez-Cruz ◽

Katiuska Gonzalez-Arzola ◽

Antonio Diaz-Quintana ◽

Irene Diaz-Moreno ◽

...

Keyword(s):

Optical Tweezers ◽

Single Molecule ◽

Molecular Level ◽

Eukaryotic Cell ◽

Histone Chaperone ◽

Histone Chaperones ◽

Dynamic Nature ◽

Nucleosome Remodeling ◽

Molecular Action ◽

Core Histones

Chromatin homeostasis mediates some of the most fundamental processes in the eukaryotic cell. In this regard, histone chaperones have emerged as major regulatory factors during DNA replication, repair, and transcription. However, the dynamic nature of these processes has severely impeded their characterization at the molecular level. Here we apply single-molecule probing by fluorescence optical tweezers to follow histone chaperone dynamics in real-time. The molecular action of SET/template-activating factor-Iβ and nucleophosmin 1, representing the two most common histone chaperone folds, were examined using both nucleosomes and isolated core histones. We show that these chaperones present binding specificity for partially dismantled nucleosomes and are able to recognize and disrupt non-native histone-DNA interactions. Furthermore, we reveal that cytochrome c inhibition of histone chaperones is coupled to chaperone accumulation on DNA-bound histones. Our single-molecule approach shows that despite the drastically different structures of these chaperones, they present conserved modes of action mediating nucleosome remodeling.

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Importin-9 wraps around the H2A-H2B core to act as nuclear importer and histone chaperone

eLife ◽

10.7554/elife.43630 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 8

Author(s):

Abhilash Padavannil ◽

Prithwijit Sarkar ◽

Seung Joong Kim ◽

Tolga Cagatay ◽

Jenny Jiou ◽

...

Keyword(s):

Crystal Structure ◽

Quantitative Analysis ◽

Nuclear Import ◽

Histone Chaperone ◽

Minor Role ◽

Deletion Mutants ◽

Histone Chaperones ◽

The Core ◽

A Minor ◽

Import Receptor

We report the crystal structure of nuclear import receptor Importin-9 bound to its cargo, the histones H2A-H2B. Importin-9 wraps around the core, globular region of H2A-H2B to form an extensive interface. The nature of this interface coupled with quantitative analysis of deletion mutants of H2A-H2B suggests that the NLS-like sequences in the H2A-H2B tails play a minor role in import. Importin-9•H2A-H2B is reminiscent of interactions between histones and histone chaperones in that it precludes H2A-H2B interactions with DNA and H3-H4 as seen in the nucleosome. Like many histone chaperones, which prevent inappropriate non-nucleosomal interactions, Importin-9 also sequesters H2A-H2B from DNA. Importin-9 appears to act as a storage chaperone for H2A-H2B while escorting it to the nucleus. Surprisingly, RanGTP does not dissociate Importin-9•H2A-H2B but assembles into a RanGTP•Importin-9•H2A-H2B complex. The presence of Ran in the complex, however, modulates Imp9-H2A-H2B interactions to facilitate its dissociation by DNA and assembly into a nucleosome.

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Epigenetics and aging

Science Advances ◽

10.1126/sciadv.1600584 ◽

2016 ◽

Vol 2 (7) ◽

pp. e1600584 ◽

Cited By ~ 246

Author(s):

Sangita Pal ◽

Jessica K. Tyler

Keyword(s):

Life Span ◽

Posttranslational Modifications ◽

Noncoding Rna ◽

Replicative Senescence ◽

Genetic Material ◽

Histone Variants ◽

Model Organisms ◽

Epigenetic Changes ◽

Epigenetic Information ◽

New Findings

Over the past decade, a growing number of studies have revealed that progressive changes to epigenetic information accompany aging in both dividing and nondividing cells. Functional studies in model organisms and humans indicate that epigenetic changes have a huge influence on the aging process. These epigenetic changes occur at various levels, including reduced bulk levels of the core histones, altered patterns of histone posttranslational modifications and DNA methylation, replacement of canonical histones with histone variants, and altered noncoding RNA expression, during both organismal aging and replicative senescence. The end result of epigenetic changes during aging is altered local accessibility to the genetic material, leading to aberrant gene expression, reactivation of transposable elements, and genomic instability. Strikingly, certain types of epigenetic information can function in a transgenerational manner to influence the life span of the offspring. Several important conclusions emerge from these studies: rather than being genetically predetermined, our life span is largely epigenetically determined; diet and other environmental influences can influence our life span by changing the epigenetic information; and inhibitors of epigenetic enzymes can influence life span of model organisms. These new findings provide better understanding of the mechanisms involved in aging. Given the reversible nature of epigenetic information, these studies highlight exciting avenues for therapeutic intervention in aging and age-associated diseases, including cancer.

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Modulation of Histone Deposition by the Karyopherin Kap114

Molecular and Cellular Biology ◽

10.1128/mcb.25.5.1764-1778.2005 ◽

2005 ◽

Vol 25 (5) ◽

pp. 1764-1778 ◽

Cited By ~ 27

Author(s):

Nima Mosammaparast ◽

Brian C. Del Rosario ◽

Lucy F. Pemberton

Keyword(s):

Nuclear Import ◽

Histone Chaperone ◽

Chromatin Assembly ◽

Histone Binding ◽

Coordinate Regulation ◽

Biochemical Evidence ◽

Secondary Role ◽

Histone Deposition

ABSTRACT The nuclear import of histones is a prerequisite for the downstream deposition of histones to form chromatin. However, the coordinate regulation of these processes remains poorly understood. Here we demonstrate that Kap114p, the primary karyopherin/importin responsible for the nuclear import of histones H2A and H2B, modulates the deposition of histones H2A and H2B by the histone chaperone Nap1p. We show that a complex comprising Kap114p, histones H2A and H2B, and Nap1p is present in the nucleus and that the presence of this complex is specifically promoted by Nap1p. This places Kap114p in a position to modulate Nap1p function, and we demonstrate by the use of two different assay systems that Kap114p inhibits Nap1p-mediated chromatin assembly. The inhibition of H2A and H2B deposition by Kap114p results in the concomitant inhibition of RCC1 loading onto chromatin. Biochemical evidence suggests that the mechanism by which Kap114p modulates histone deposition primarily involves direct histone binding, while the interaction between Kap114p and Nap1p plays a secondary role. Furthermore, we found that the inhibition of histone deposition by Kap114p is partially reversed by RanGTP. Our results indicate a novel mechanism by which cells can regulate histone deposition and establish a coordinate link between histone nuclear import and chromatin assembly.

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Histone transfer among chaperones

Biochemical Society Transactions ◽

10.1042/bst20110737 ◽

2012 ◽

Vol 40 (2) ◽

pp. 357-363 ◽

Cited By ~ 17

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.

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Epigenetic reprogramming and chromatin accessibility in pediatric diffuse intrinsic pontine gliomas: a neural developmental disease

Neuro-Oncology ◽

10.1093/neuonc/noz218 ◽

2019 ◽

Vol 22 (2) ◽

pp. 195-206 ◽

Cited By ~ 1

Author(s):

Flor M Mendez ◽

Felipe J Núñez ◽

Maria B Garcia-Fabiani ◽

Santiago Haase ◽

Stephen Carney ◽

...

Keyword(s):

Histone Variants ◽

Diffuse Intrinsic Pontine Glioma ◽

Chromatin Accessibility ◽

Therapeutic Implications ◽

Polycomb Repressive Complex 2 ◽

K27m Mutation ◽

Histone 3 ◽

Epigenetic Programming ◽

Genes Encoding ◽

Diffuse Intrinsic Pontine Gliomas

Abstract Diffuse intrinsic pontine glioma (DIPG) is a rare but deadly pediatric brainstem tumor. To date, there is no effective therapy for DIPG. Transcriptomic analyses have revealed DIPGs have a distinct profile from other pediatric high-grade gliomas occurring in the cerebral hemispheres. These unique genomic characteristics coupled with the younger median age group suggest that DIPG has a developmental origin. The most frequent mutation in DIPG is a lysine to methionine (K27M) mutation that occurs on H3F3A and HIST1H3B/C, genes encoding histone variants. The K27M mutation disrupts methylation by polycomb repressive complex 2 on histone H3 at lysine 27, leading to global hypomethylation. Histone 3 lysine 27 trimethylation is an important developmental regulator controlling gene expression. This review discusses the developmental and epigenetic mechanisms driving disease progression in DIPG, as well as the profound therapeutic implications of epigenetic programming.

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