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BBA - Gene Regulatory Mechanisms (v.1819, #3-4)
Assembling chromatin: The long and winding road by Anthony T. Annunziato (pp. 196-210).
It has been over 35years since the acceptance of the “chromatin subunit” hypothesis, and the recognition that nucleosomes are the fundamental repeating units of chromatin fibers. Major subjects of inquiry in the intervening years have included the steps involved in chromatin assembly, and the chaperones that escort histones to DNA. The following commentary offers an historical perspective on inquiries into the processes by which nucleosomes are assembled on replicating and nonreplicating chromatin. This article is part of a Special Issue entitled: Histone chaperones and Chromatin assembly.► An historical perspective of the chromatin assembly field is presented. ► Early investigations into nucleosome assembly and histone segregation are discussed. ► Initial attempts to identify chromatin assembly factors are highlighted.
Keywords: Chromatin; Replication; Assembly; Histone; Chaperone; Factor
Towards a mechanism for histone chaperones by Elsasser Simon J. Elsässer; Sheena D'Arcy (pp. 211-221).
Histone chaperones can be broadly defined as histone-binding proteins that influence chromatin dynamics in an ATP-independent manner. Their existence reflects the importance of chromatin homeostasis and the unique and unusual biochemistry of the histone proteins. Histone supply and demand at chromatin is regulated by a network of structurally and functionally diverse histone chaperones. At the core of this network is a mechanistic variability that is only beginning to be appreciated. In this review, we highlight the challenges in determining histone chaperone mechanism and discuss possible mechanisms in the context of nucleosome thermodynamics. We discuss how histone chaperones prevent promiscuous histone interactions, and consider if this activity represents the full extent of histone chaperone function in governing chromatin dynamics. This article is part of a Special Issue entitled: Histone chaperones and Chromatin assembly.► The unique biochemistry of histones causes a requirement for histone chaperones. ► Histone chaperones are histone-binding proteins that facilitate nucleosome assembly. ► Histone chaperones are structurally, functionally and mechanistically diverse. ► Histone chaperones prevent non-specific histone interactions. ► Histone chaperones adopt diverse histone-binding modes.
Keywords: Abbreviations; ATRX; Alpha Thalassemia/mental retardation syndrome X-linked; Asf1; Anti-silencing Function 1; cenH3; centromeric H3; Chz1; Chaperone for Htz1/H2A-H2B dimer 1; CAF1; Chromatin Assembly Factor 1; DAXX; Death-domain Associated protein; FACT; Facilitates Chromatin Transcription; HIRA; HIR histone cell cycle regulation defective homolog A; HJURP; Holliday Junction Recognition Protein; Nap1; Nuclear assembly protein 1; NASP; Nuclear Autoantigenic Sperm Protein; NPM; Nucleosplasmin; ptms; post-translational modifications; Rtt106; Regulator of Ty1 Transposition 106; Rtt109; Regulator of Ty1 Transposition 109; RbAp46/48; Retinoblastoma binding protein 7/4 46/48; SET1; SET domain-containing 1; SWR1; SWI/SNF-related protein; SSRP1; Structure Specific Recognition Protein 1; Scm3; Suppressor of chromosome mic-segregation 3; SPT16; Suppressor of Ty 16 homolog; Vps75; Vacuolar Protein Sorting 75Histone; Histone variant; Histone chaperone; Nucleosome; Chromatin; Thermodynamics
Histone variants and epigenetic inheritance by Gang Yuan; Bing Zhu (pp. 222-229).
Nucleosome particles, which are composed of core histones and DNA, are the basic unit of eukaryotic chromatin. Histone modifications and histone composition determine the structure and function of the chromatin; this genome packaging, often referred to as “epigenetic information”, provides additional information beyond the underlying genomic sequence. The epigenetic information must be transmitted from mother cells to daughter cells during mitotic division to maintain the cell lineage identity and proper gene expression. However, the mechanisms responsible for mitotic epigenetic inheritance remain largely unknown. In this review, we focus on recent studies regarding histone variants and discuss the assembly pathways that may contribute to epigenetic inheritance. This article is part of a Special Issue entitled: Histone chaperones and Chromatin assembly.► Which histone variants may play a role in epigenetic inheritance? ► What kind of characteristic genome distributions of histone variants may be involved in epigenetic inheritance? ► How do histone variants contribute to epigenetic inheritance?
Keywords: Histone variant; Epigenetics; Chromatin
Chaperoning the histone H3 family by Ali Hamiche; Muhammad Shuaib (pp. 230-237).
Chromatin is a highly dynamic nucleoprotein structure, which orchestrates all nuclear process from DNA replication to DNA repair, from transcription to recombination. The proper in vivo assembly of nucleosome, the basic repeating unit of chromatin, requires the deposition of two H3–H4 dimer pairs followed by the addition of two dimers of H2A and H2B. Histone chaperones are responsible for delivery of histones to the site of chromatin assembly and histone deposition onto DNA, histone exchange and removal. Distinct factors have been found associated with different histone H3 variants, which facilitate their deposition. Unraveling the mechanism of histone deposition by specific chaperones is of key importance to epigenetic regulation. In this review, we focus on histone H3 variants and their deposition mechanisms. This article is part of a Special Issue entitled:Histone chaperones and Chromatin assembly.► In this review, we focus on the mechanism of histone H3 variants deposition. ► We highlight the role of histone chaperones in their incorporation to chromatin. ► We discuss how H3 variants contribute to marking specific chromosomal domains.
Keywords: Histone variants; Histone chaperones, chromatin assembly
All roads lead to chromatin: Multiple pathways for histone deposition by Qing Li; Rebecca Burgess; Zhiguo Zhang (pp. 238-246).
Chromatin, a complex of DNA and associated proteins, governs diverse processes including gene transcription, DNA replication and DNA repair. The fundamental unit of chromatin is the nucleosome, consisting of 147bp of DNA wound about 1.6 turns around a histone octamer of one (H3–H4)2 tetramer and two H2A–H2B dimers. In order to form nucleosomes, (H3–H4)2 tetramers are deposited first, followed by the rapid deposition of H2A–H2B. It is believed that the assembly of (H3–H4)2 tetramers into nucleosomes is the rate-limiting step of nucleosome assembly. Moreover, assembly of H3–H4 into nucleosomes following DNA replication, DNA repair and gene transcription is likely to be a key step in the inheritance of epigenetic information and maintenance of genome integrity. In this review, we discuss how nucleosome assembly of H3–H4 is regulated by concerted actions of histone chaperones and modifications on newly synthesized H3 and H4. This article is part of a Special Issue entitled: Histone chaperones and Chromatin assembly.► We review the literature on replication‐coupled and replication‐independent nucleosome assembly. ► We highlight the functions of histone chaperones in nucleosome assembly. ► We discuss the roles of histone modifications in nucleosome assembly. ► We speculate the future direction of the nucleosome assembly field.
Keywords: Nucleosome assembly; Histone modification; Histone chaperone; HIRA; CAF-1; Rtt106
The role of FACT in making and breaking nucleosomes by Tim Formosa (pp. 247-255).
FACT is a roughly 180kDa heterodimeric protein complex important for managing the properties of chromatin in eukaryotic cells. Chromatin is a repressive barrier that plays an important role in protecting genomic DNA and regulating access to it. This barrier must be temporarily removed during transcription, replication, and repair, but it also must be rapidly restored to the original state afterwards. Further, the properties of chromatin are dynamic and must be adjusted as conditions dictate. FACT was identified as a factor that destabilizes nucleosomes in vitro, but it has now also been implicated as a central factor in the deposition of histones to form nucleosomes, as an exchange factor that swaps the histones within existing nucleosomes for variant forms, and as a tether that prevents histones from being displaced by the passage of RNA polymerases during transcription. FACT therefore plays central roles in building, maintaining, adjusting, and overcoming the chromatin barrier. This review summarizes recent results that have begun to reveal how FACT can promote what appear to be contradictory goals, using a simple set of binding activities to both enhance and diminish the stability of nucleosomes. This article is part of a Special Issue entitled: Histone chaperones and Chromatin assembly.► FACT has a modular domain organization, allowing simultaneous contact with multiple histones or other proteins. ► FACT either induces or captures a reorganized nucleosome form that is more open than the canonical structure. ► Nucleosome reorganization promotes initiation and elongation of transcription and replication. ► FACT can destabilize nucleosomes but it also tethers the components together for reassembly, promoting nucleosome stability. ► FACT may have a central role in de novo nucleosome assembly during DNA replication.
Keywords: Spt16; Pob3; Nucleosome reorganization; Histone chaperone
Histone acetyltransferase 1: More than just an enzyme? by Mark R. Parthun (pp. 256-263).
Histone acetyltransferase 1 (HAT1) is an enzyme that is likely to be responsible for the acetylation that occurs on lysines 5 and 12 of the NH2-terminal tail of newly synthesized histone H4. Initial studies suggested that, despite its evolutionary conservation, this modification of new histone H4 played only a minor role in chromatin assembly. However, a number of recent studies have brought into focus the important role of both this modification and HAT1 in histone dynamics. Surprisingly, the function of HAT1 in chromatin assembly may extend beyond just its catalytic activity to include its role as a major histone binding protein. These results are incorporated into a model for the function of HAT1 in histone deposition and chromatin assembly. This article is part of a Special Issue entitled: Histone chaperones and Chromatin assembly.► Discussion of recent advances in our understanding of the type B histone acetyltransferase Hat1. ► Hat1 acetylates newly synthesized histone H4 at lysines 5 and 12. ► Hat1 and its complexes have been found to be major binding partners of soluble histones H3 and H4. ► A model proposed for the activities of Hat1 complexes in the process of chromatin assembly.
Keywords: HAT1; HAT2; NASP; Chromatin assembly; Histone chaperone; Histone acetylation
A global requirement for the HIR complex in the assembly of chromatin by Amit Dipak Amin; Nidhi Vishnoi; Philippe Prochasson (pp. 264-276).
Due to its extensive length, DNA is packaged into a protective chromatin structure known as the nucleosome. In order to carry out various cellular functions, nucleosomes must be disassembled, allowing access to the underlying DNA, and subsequently reassembled on completion of these processes. The assembly and disassembly of nucleosomes is dependent on the function of histone modifiers, chromatin remodelers and histone chaperones. In this review, we discuss the roles of an evolutionarily conserved histone chaperone known as the HIR/HIRA complex. In S. cerevisiae, the HIR complex is made up of the proteins Hir1, Hir2, Hir3 and Hpc2, which collectively act in transcriptional regulation, elongation, gene silencing, cellular senescence and even aging. This review presents an overview of the role of the HIR complex, in yeast as well as other organisms, in each of these processes, in order to give a better understanding of how nucleosome assembly is imperative for cellular homeostasis and genomic integrity. This article is part of a Special Issue entitled: Histone chaperones and Chromatin assembly.► A global requirement for the HIR complex in the assembly of chromatin ► HIR regulates the histone genes during the cell cycle. ► HIR nucleosome assembly activity is important for the stability of the genome ► Interaction between HIR, Asf1 and Rtt106 in regulating chromatin structure ► Implication of HIRA in senescence, aging, disease and development.
Keywords: HIR1; HIR2; HIR3; HPC2; HIRA; Histone chaperone
Histone chaperones link histone nuclear import and chromatin assembly by Kristin M. Keck; Lucy F. Pemberton (pp. 277-289).
Histone chaperones are proteins that shield histones from nonspecific interactions until they are assembled into chromatin. After their synthesis in the cytoplasm, histones are bound by different histone chaperones, subjected to a series of posttranslational modifications and imported into the nucleus. These evolutionarily conserved modifications, including acetylation and methylation, can occur in the cytoplasm, but their role in regulating import is not well understood. As part of histone import complexes, histone chaperones may serve to protect the histones during transport, or they may be using histones to promote their own nuclear localization. In addition, there is evidence that histone chaperones can play an active role in the import of histones. Histone chaperones have also been shown to regulate the localization of important chromatin modifying enzymes. This review is focused on the role histone chaperones play in the early biogenesis of histones, the distinct cytoplasmic subcomplexes in which histone chaperones have been found in both yeast and mammalian cells and the importins/karyopherins and nuclear localization signals that mediate the nuclear import of histones. We also address the role that histone chaperone localization plays in human disease. This article is part of a Special Issue entitled: Histone chaperones and chromatin assembly.► Evolutionarily conserved karyopherins import histones and histone chaperones. ► Cytoplasmic histones are acetylated and monomethylated on the amino-terminal tail. ► Newly synthesized histones form cytoplasmic complexes with histone chaperones. ► Histone chaperones can promote import of histones and chromatin modifying enzymes. ► Misregulation or mislocalization of histone chaperones is associated with cancer.
Keywords: Histone chaperone; Importin; Histone acetylation; Asf1; Nap1; NASP
Precise deposition of histone H2A.Z in chromatin for genome expression and maintenance by Pierre Billon; Cote Jacques Côté (pp. 290-302).
Histone variant H2A.Z is essential in higher eukaryotes and has different functions in the cell. Several studies indicate that H2A.Z is found at specific loci in the genome such as regulatory-gene regions, where it poises genes for transcription. Its deposition creates chromatin regions with particular structural characteristics which could favor rapid transcription activation. This review focuses on the highly regulated mechanism of H2A.Z deposition in chromatin which is essential for genome integrity. Chaperones escort H2A.Z to large ATP-dependent chromatin remodeling enzymes which are responsible for its deposition/eviction. Over the last ten years, biochemical, genetic and genomic studies helped us understand the precise role of these complexes in this process. It has been suggested that a cooperation occurs between histone acetyltransferase and chromatin remodeling activities to incorporate H2A.Z in chromatin. Its regulated deposition near centromeres and telomeres also shows its implication in chromosomal structure integrity and parallels a role in DNA damage response. The dynamics of H2A.Z deposition/eviction at specific loci was shown to be critical for genome expression and maintenance, thus cell fate. Altogether, recent findings reassert the importance of the regulated deposition of this histone variant. This article is part of a Special Issue entitled: Histone chaperones and Chromatin assembly.► Histone variant H2A.Z is implicated in genome expression and maintenance. ► H2A.Z has a very distinct mechanism of deposition/eviction on chromatin. ► Chromatin modifications regulate H2A.Z incorporation.
Keywords: Histone variant; H2A.Z; Htz1; SWR1; INO80; p400; SRCAP; Chz1; NuA4
Cell cycle regulation of silent chromatin formation by Tiffany J. Young; Ann L. Kirchmaier (pp. 303-312).
Identical genes in two different cells can stably exist in alternate transcriptional states despite the dynamic changes that will occur to chromatin at that locus throughout the cell cycle. In mammals, this is achieved through epigenetic processes that regulate key developmental transitions and ensure stable patterns of gene expression during growth and differentiation. The budding yeast Saccharomyces cerevisiae utilizes silencing to control the expression state of genes encoding key regulatory factors for determining cell-type, ribosomal RNA levels and proper telomere function. Here, we review the composition of silent chromatin in S. cerevisiae, how silent chromatin is influenced by chromatin assembly and histone modifications and highlight several observations that have contributed to our understanding of the interplay between silent chromatin formation and stability and the cell cycle. This article is part of a Special Issue entitled: Histone chaperones and Chromatin assembly.► Histone modifications, chromatin assembly and replication influence silent chromatin. ► The establishment of silencing is regulated during the cell cycle. ► The stability of silent chromatin varies during the cell cycle. ► Silencers affect establishment and enhance the stability of silent chromatin. ► Promoter, cohesin and locus-specific effects on the establishment of silencing exist.
Keywords: Abbreviations; S. cerevisiae; Sacchromyces cerevisiae; ORC; Origin Recognition Complex; SIR; Silent Information Regulator; HMR-E; E; silencer at; HMR; HML-E; E; silencer at; HMLSilencing; Epigenetic; SIR1; SIR2; SIR3; SIR4
Centromeric chromatin and the pathway that drives its propagation by Samantha J. Falk; Ben E. Black (pp. 313-321).
The centromere is the locus that directs chromosomal inheritance at cell division. While centromeres in diverse eukaryotes are commonly found at sites of repetitive DNA, their location is epigenetically specified. The histone H3 variant CENP-A is the prime candidate for epigenetically marking the centromere, and recent work has uncovered several additional proteins that play key roles in centromere assembly and maintenance. We describe advances in the identification and characterization of proteins that form the centromere, and focus on recent findings that have advanced our understanding of the assembly of functional centromeric chromatin. This article is part of a Special Issue entitled: Histone chaperones and chromatin assembly.► Structure of CENP-A complexes provide insight into centromere function and propagation. ► The levels of CENP-A present at the centromere change with the cell cycle. ► The CENP-A deposition pathway during G1 requires distinct steps. ► S phase CENP-A redeposition may occur with or without the assistance of chaperones.
Keywords: CENP-A; Centromere; Kinetochore; Histone variant; Cell cycle; HJURP
Lessons from senescence: Chromatin maintenance in non-proliferating cells by Taranjit Singh Rai; Peter D. Adams (pp. 322-331).
Cellular senescence is an irreversible proliferation arrest, thought to contribute to tumor suppression, proper wound healing and, perhaps, tissue and organismal aging. Two classical tumor suppressors, p53 and pRB, control cell cycle arrest associated with senescence. Profound molecular changes occur in cells undergoing senescence. At the level of chromatin, for example, senescence associated heterochromatic foci (SAHF) form in some cell types. Chromatin is inherently dynamic and likely needs to be actively maintained to achieve a stable cell phenotype. In proliferating cells chromatin is maintained in conjunction with DNA replication, but how non-proliferating cells maintain chromatin structure is poorly understood. Some histone variants, such as H3.3 and macroH2A increase as cells undergo senescence, suggesting histone variants and their associated chaperones could be important in chromatin structure maintenance in senescent cells. Here, we discuss options available for senescent cells to maintain chromatin structure and the relative contribution of histone variants and chaperones in this process. This article is part of a Special Issue entitled: Histone chaperones and chromatin assembly.► Overview of cell senescence. ► Overview of chromatin structure. ► Implications of senescence for chromatin maintenance. ► Model for maintenance of chromatin structure in senescence.
Keywords: Senescence; Chromatin
Histone exchange and histone modifications during transcription and aging by Chandrima Das; Jessica K. Tyler (pp. 332-342).
The organization of the eukaryotic genome into chromatin enables DNA to fit inside the nucleus while also regulating the access of proteins to the DNA to facilitate genomic functions such as transcription, replication and repair. The basic repeating unit of chromatin is the nucleosome, which includes 147bp of DNA wrapped 1.65 times around an octamer of core histone proteins comprising two molecules each of H2A, H2B, H3 and H4 [1]. Each nucleosome is a highly stable unit, being maintained by over 120 direct protein–DNA interactions and several hundred water mediated ones [1]. Accordingly, there is considerable interest in understanding how processive enzymes such as RNA polymerases manage to pass along the coding regions of our genes that are tightly packaged into arrays of nucleosomes. Here we present the current mechanistic understanding of this process and the evidence for profound changes in chromatin dynamics during aging. This article is part of a Special Issue entitled: Histone chaperones and Chromatin assembly.► We review the evidence for histone exchange during RNA polymerase passage. ► We summarize the mechanistic understanding of this process. ► We discuss the role of histone modifications in this process. ► Organismal aging is accompanied by changes in chromatin dynamics.
Keywords: Histone chaperone; Histone modification; Aging; Lifespan extension; Chromatin; Transcription
Histone variants and chromatin assembly in plant abiotic stress responses by Yan Zhu; Aiwu Dong; Wen-Hui Shen (pp. 343-348).
Genome organization into nucleosomes and higher-order chromatin structures has profound implications for the regulation of gene expression, DNA replication and repair. The structure of chromatin can be remodeled by several mechanisms; among others, nucleosome assembly/disassembly and replacement of canonical histones with histone variants constitute important ones. In this review, we provide a brief description on the current knowledge about histone chaperones involved in nucleosome assembly/disassembly and histone variants in Arabidopsis thaliana. We discuss recent advances in revealing crucial functions of histone chaperones, nucleosome assembly/disassembly and histone variants in plant response to abiotic stresses. It appears that chromatin structure remodeling may provide a flexible, global and stable means for the regulation of gene transcription to help plants more effectively cope with environmental stresses. This article is part of a Special Issue entitled: Histone chaperones and chromatin assembly.► Histone variants and nucleosome assembly. ► Genotoxic stress and genome stability. ► Stress-induced transcription and modifications of nucleosome occupancy and histone variant incorporation.
Keywords: Histone variant; Histone chaperone; Chromatin remodeling; Epigenetics; Abiotic stress; Arabidopsis thaliana
Chromatin-mediated Candida albicans virulence by Jessica Lopes da Rosa; Paul D. Kaufman (pp. 349-355).
Candida albicans is the most prevalent human fungal pathogen. To successfully propagate an infection, this organism relies on the ability to change morphology, express virulence-associated genes and resist DNA damage caused by the host immune system. Many of these events involve chromatin alterations that are crucial for virulence. This review will focus on the studies that have been conducted on how chromatin function affects pathogenicity of C. albicans and other fungi. This article is part of a Special Issue entitled: Histone chaperones and Chromatin assembly.► We review studies that address chromatin modifications and pathogenicity in Candida albicans. ► Resistance to DNA damage from reactive oxygen species is vital to C. albicans pathogenicity. ► We highlight RTT109 and H3K56 acetylation as major factors in promoting pathogenicity. ► Several other chromatin-regulating pathways are also critical for pathogenicity. ► We conclude that fungal-specific chromatin proteins should be targets for novel anti-fungal agents.
Keywords: Candida albicans; Rtt109; Histone H3 lysine 56; Chromatin modification; DNA damage; Fungal pathogen