Histones and their chaperones: Adaptive remodelers of an ever-changing chromatinic landscape (original) (raw)
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Histone Chaperones: Functions beyond Nucleosome Deposition
Advances in Bioscience and Biotechnology, 2014
Histones, the structural unit of chromatin, must be assembled/dissembled to preserve or change chromatin organization in accordance to cellular needs. Initially, function of histone chaperones was thought to be only "histone carriers/vehicles", but now with accumulating evidences they are known to be the key actors of histone metabolism. With this outburst of knowledge, histone chaperones are now placed at the center of gene regulation, having roles to play in DNA replication, repair and transcription. This review will focus on the current knowledge we have about the role of histone chaperones in regulating cellular processes and their relation to disease. In addition, we discuss the potential of histone chaperones as a therapeutic target.
Histone chaperones, a supporting role in the limelight
Biochimica Et Biophysica Acta-gene Structure and Expression, 2004
In eukaryotic cells, highly basic histone proteins are associated with the DNA to form the nucleosome, the fundamental unit of chromatin. Histones are closely escorted by histone chaperones from their point of synthesis up to their delivery site. We will present an overview of the histone chaperones identified to date with their various roles, in an attempt to highlight their importance in cellular metabolism. Nucleoplasmin will illustrate a role in histone storage and Nap-1, a histone translocator. CAF-1 and Hira will provide examples of distinct histone deposition factors coupled to and uncoupled from DNA synthesis, respectively, while Asf1 could act as a histone donor. We then will illustrate with two examples how histone chaperones can be associated with chromatin remodeling activities. Finally, we will discuss how the RbAp46/48 proteins, as escort factors, are part of multiple complexes with various functions. Based on these examples, we will propose a scheme in which the diverse roles of histone chaperones are integrated within an assembly line for chromatin formation and regulation. Finally, we discuss how these chaperones may have more than a supporting role in a histone metabolic pathway. D
The histone shuffle: histone chaperones in an energetic dance
Trends in Biochemical Sciences, 2010
Our genetic information is tightly packaged into a rather ingenious nucleoprotein complex called chromatin in a manner that enables it to be rapidly accessed during genomic processes. Formation of the nucleosome, which is the fundamental unit of chromatin, occurs via a stepwise process that is reversed to enable the disassembly of nucleosomes. Histone chaperone proteins have prominent roles in facilitating these processes as well as in replacing old histones with new canonical histones or histone variants during the process of histone exchange. Recent structural, biophysical and biochemical studies have begun to shed light on the molecular mechanisms whereby histone chaperones promote chromatin assembly, disassembly and histone exchange to facilitate DNA replication, repair and transcription.
Essential histone chaperones collaborate to regulate transcription and chromatin integrity
SUMMARYHistone chaperones are critical for controlling chromatin integrity during transcription, DNA replication, and DNA repair. We have discovered that the physical interaction between two essential histone chaperones, Spt6 and Spn1/Iws1, is required for transcriptional accuracy and nucleosome organization. To understand this requirement, we have isolated suppressors of an spt6 mutation that disrupts the Spt6-Spn1 interaction. Several suppressors are in a third essential histone chaperone, FACT, while another suppressor is in the transcription elongation factor Spt5/DSIF. The FACT suppressors weaken FACT-nucleosome interactions and bypass the requirement for Spn1, possibly by restoring a necessary balance between Spt6 and FACT on chromatin. In contrast, the Spt5 suppressor modulates Spt6 function in a Spn1-dependent manner. Despite these distinct mechanisms, both suppressors alleviate the nucleosome organization defects caused by disruption of the Spt6-Spn1 interaction. Taken toge...
Clothing up DNA for all seasons: Histone chaperones and nucleosome assembly pathways
FEBS Letters, 2008
In eukaryotes, the packaging of DNA into chromatin is essential for cell viability. Several important DNA metabolic events require the transient disruption of chromatin structure, but cells have evolved a number of elaborate pathways that operate throughout the cell cycle to prevent the deleterious effects of chromatin erosion. In this review, we describe a number of distinct nucleosome assembly pathways that function during DNA replication, transcription, cellular senescence and early embryogenesis. In addition, we illustrate some of the physiological consequences associated with defects in nucleosome assembly pathways.
Annual Review of Cell and Developmental Biology, 2014
Within the nucleus, the interplay between lineage-specific transcription factors and chromatin dynamics defines cellular identity. Control of this interplay is necessary to properly balance stability and plasticity during the development and entire life span of multicellular organisms. Here, we present our current knowledge of the contribution of histone H3 variants to chromatin dynamics during development. We review the network of histone chaperones that governs their deposition timing and sites of incorporation and highlight how their distinct distribution impacts genome organization and function. We integrate the importance of H3 variants in the context of nuclear reprogramming and cell differentiation, and, using the centromere as a paradigm, we describe a case in which the identity of a given genomic locus is propagated across different cell types. Finally, we compare development to changes in stress and disease. Both physiological and pathological settings underline the importance of H3 dynamics for genome and chromatin integrity.
Histone chaperones: an escort network regulating histone traffic
Nature Structural & Molecular Biology, 2007
In eukaryotes, DNA is organized into chromatin in a dynamic manner that enables it to be accessed for processes such as transcription and repair. Histones, the chief protein component of chromatin, must be assembled, replaced or exchanged to preserve or change this organization according to cellular needs. Histone chaperones are key actors during histone metabolism. Here we classify known histone chaperones and discuss how they build a network to escort histone proteins. Molecular interactions with histones and their potential specificity or redundancy are also discussed in light of chaperone structural properties. The multiplicity of histone chaperone partners, including histone modifiers, nucleosome remodelers and cell-cycle regulators, is relevant to their coordination with key cellular processes. Given the current interest in chromatin as a source of epigenetic marks, we address the potential contributions of histone chaperones to epigenetic memory and genome stability.
Chaperone control of the activity and specificity of the histone H3 acetyltransferase Rtt109
Molecular and cellular biology, 2008
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 rtt109Delta 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 ...
Histone exchange and histone modifications during transcription and aging
Biochimica Et Biophysica Acta-gene Regulatory Mechanisms
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 147 bp of DNA wrapped 1.65 times around an octamer of core histone proteins comprising two molecules each of H2A, H2B, H3 and H4 . 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. j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / b b a g r m
Chaperoning the histone H3 family
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 2012
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.