The Experts below are selected from a list of 258 Experts worldwide ranked by ideXlab platform
Steven Henikoff - One of the best experts on this subject based on the ideXlab platform.
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Histone variants — ancient wrap artists of the epigenome
Nature Reviews Molecular Cell Biology, 2010Co-Authors: Paul B. Talbert, Steven HenikoffAbstract:Histones wrap DNA to form nucleosome particles that compact eukaryotic genomes. Variant Histones have evolved crucial roles in chromosome segregation, transcriptional regulation, DNA repair, sperm packaging and other processes. 'Universal' histone variants emerged early in eukaryotic evolution and were later displaced for bulk packaging roles by the canonical Histones (H2A, H2B, H3 and H4), the synthesis of which is coupled to DNA replication. Further specializations of histone variants have evolved in some lineages to perform additional tasks. Differences among histone variants in their stability, DNA wrapping, specialized domains that regulate access to DNA, and post-translational modifications, underlie the diverse functions that Histones have acquired in evolution. Histone core particles are spools for wrapping DNA, whereas histone variants have evolved diverse additional roles in chromosome metabolism. Some variants mediate universal functions, such as chromosome segregation and DNA repair, and others specialize in organism-specific tasks. Canonical Histones H2A, H2B, H3 and H4 wrap DNA to form nucleosome particles that compact the genome. Histone variants have diverse additional roles in chromosome metabolism and can differ from canonical Histones in stability, DNA wrapping and specialized domains. The 'universal' variants, centromeric histone variant H3 (CenH3), H3.3, H2A.Z and H2A.X, appeared before the divergence of modern eukaryotes and function in common eukaryotic cellular processes such as histone replacement, chromosome segregation, DNA repair, and transcriptional regulation. Specialized Histones have arisen in some lineages to perform additional tasks. Centromeric nucleosomes contain CenH3 and form the essential foundation of the kinetochore. The subunit composition of the CenH3 histone core has been the subject of lively debate and it has been found to wrap DNA in a right-handed direction, opposite to that of ordinary nucleosomes. H2A.Z has a conserved role in transcription initiation that might be descended from a hypothetical ancient mode of gene regulation by histone variants found in modern trypanosomes. Dynamic cellular processes might dramatically alter the stability of H2A.Z nucleosomes and thereby facilitate transcription initiation. Chromatin must be remodelled in processes such as DNA repair and sex chromosome silencing. Variants H2A.X and H3.3 have prominent roles in remodelling, with specialized sperm Histones and protamines mediating sperm packaging and decondensation. Lineage-specific H2A variants have diverse carboxy-terminal tails that can wrap more DNA with additional oligopeptide motifs, or less DNA with a shorter docking domain. They sometimes have non-histone domains, which in macroH2As inhibit polyADP-ribosylation and contribute to conditional gene silencing.
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histone variants ancient wrap artists of the epigenome
Nature Reviews Molecular Cell Biology, 2010Co-Authors: Paul B. Talbert, Steven HenikoffAbstract:Histones wrap DNA to form nucleosome particles that compact eukaryotic genomes. Variant Histones have evolved crucial roles in chromosome segregation, transcriptional regulation, DNA repair, sperm packaging and other processes. 'Universal' histone variants emerged early in eukaryotic evolution and were later displaced for bulk packaging roles by the canonical Histones (H2A, H2B, H3 and H4), the synthesis of which is coupled to DNA replication. Further specializations of histone variants have evolved in some lineages to perform additional tasks. Differences among histone variants in their stability, DNA wrapping, specialized domains that regulate access to DNA, and post-translational modifications, underlie the diverse functions that Histones have acquired in evolution.
Mark R. Parthun - One of the best experts on this subject based on the ideXlab platform.
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replication dependent histone isoforms a new source of complexity in chromatin structure and function
Nucleic Acids Research, 2018Co-Authors: Rajbir Singh, Emily Bassett, Arnab Chakravarti, Mark R. ParthunAbstract:Replication-dependent Histones are expressed in a cell cycle regulated manner and supply the Histones necessary to support DNA replication. In mammals, the replication-dependent Histones are encoded by a family of genes that are located in several clusters. In humans, these include 16 genes for histone H2A, 22 genes for histone H2B, 14 genes for histone H3, 14 genes for histone H4 and 6 genes for histone H1. While the proteins encoded by these genes are highly similar, they are not identical. For many years, these genes were thought to encode functionally equivalent histone proteins. However, several lines of evidence have emerged that suggest that the replication-dependent histone genes can have specific functions and may constitute a novel layer of chromatin regulation. This Survey and Summary reviews the literature on replication-dependent histone isoforms and discusses potential mechanisms by which the small variations in primary sequence between the isoforms can alter chromatin function. In addition, we summarize the wealth of data implicating altered regulation of histone isoform expression in cancer.
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Identification of replication-dependent and replication-independent linker histone complexes: Tpr specifically promotes replication-dependent linker histone stability
BMC Biochemistry, 2016Co-Authors: Pei Zhang, Owen E. Branson, Michael A. Freitas, Mark R. ParthunAbstract:Background There are 11 variants of linker histone H1 in mammalian cells. Beyond their shared abilities to stabilize and condense chromatin, the H1 variants have been found to have non-redundant functions, the mechanisms of which are not fully understood. Like core Histones, there are both replication-dependent and replication-independent linker histone variants. The histone chaperones and other factors that regulate linker histone dynamics in the cell are largely unknown. In particular, it is not known whether replication-dependent and replication-independent linker Histones interact with distinct or common sets of proteins. To better understand linker histone dynamics and assembly, we used chromatography and mass spectrometry approaches to identify proteins that are associated with replication-dependent and replication-independent H1 variants. We then used a variety of in vivo analyses to validate the functional relevance of identified interactions. Results We identified proteins that bind to all linker histone variants and proteins that are specific for only one class of variant. The factors identified include histone chaperones, transcriptional regulators, RNA binding proteins and ribosomal proteins. The nuclear pore complex protein Tpr, which was found to associate with only replication-dependent linker Histones, specifically promoted their stability. Conclusion Replication-dependent and replication-independent linker histone variants can interact with both common and distinct sets of proteins. Some of these factors are likely to function as histone chaperones while others may suggest novel links between linker Histones and RNA metabolism. The nuclear pore complex protein Tpr specifically interacts with histone H1.1 and H1.2 but not H1x and can regulate the stability of these replication-dependent linker Histones.
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Identification of replication-dependent and replication-independent linker histone complexes: Tpr specifically promotes replication-dependent linker histone stability.
BMC biochemistry, 2016Co-Authors: Pei Zhang, Owen E. Branson, Michael A. Freitas, Mark R. ParthunAbstract:There are 11 variants of linker histone H1 in mammalian cells. Beyond their shared abilities to stabilize and condense chromatin, the H1 variants have been found to have non-redundant functions, the mechanisms of which are not fully understood. Like core Histones, there are both replication-dependent and replication-independent linker histone variants. The histone chaperones and other factors that regulate linker histone dynamics in the cell are largely unknown. In particular, it is not known whether replication-dependent and replication-independent linker Histones interact with distinct or common sets of proteins. To better understand linker histone dynamics and assembly, we used chromatography and mass spectrometry approaches to identify proteins that are associated with replication-dependent and replication-independent H1 variants. We then used a variety of in vivo analyses to validate the functional relevance of identified interactions. We identified proteins that bind to all linker histone variants and proteins that are specific for only one class of variant. The factors identified include histone chaperones, transcriptional regulators, RNA binding proteins and ribosomal proteins. The nuclear pore complex protein Tpr, which was found to associate with only replication-dependent linker Histones, specifically promoted their stability. Replication-dependent and replication-independent linker histone variants can interact with both common and distinct sets of proteins. Some of these factors are likely to function as histone chaperones while others may suggest novel links between linker Histones and RNA metabolism. The nuclear pore complex protein Tpr specifically interacts with histone H1.1 and H1.2 but not H1x and can regulate the stability of these replication-dependent linker Histones.
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the human histone chaperone snasp interacts with linker and core Histones through distinct mechanisms
Nucleic Acids Research, 2012Co-Authors: Huanyu Wang, Scott T R Walsh, Mark R. ParthunAbstract:Somatic nuclear autoantigenic sperm protein (sNASP) is a human homolog of the N1/N2 family of histone chaperones. sNASP contains the domain structure characteristic of this family, which includes a large acidic patch flanked by several tetratricopeptide repeat (TPR) motifs. sNASP possesses a unique binding specificity in that it forms specific complexes with both histone H1 and Histones H3/H4. Based on the binding affinities of sNASP variants to Histones H1, H3.3, H4 and H3.3/H4 complexes, sNASP uses distinct structural domains to interact with linker and core Histones. For example, one of the acidic patches of sNASP was essential for linker histone binding but not for core histone interactions. The fourth TPR of sNASP played a critical role in interactions with histone H3/H4 complexes, but did not influence histone H1 binding. Finally, analysis of cellular proteins demonstrated that sNASP existed in distinct complexes that contained either linker or core Histones.
Paul B. Talbert - One of the best experts on this subject based on the ideXlab platform.
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Histone variants — ancient wrap artists of the epigenome
Nature Reviews Molecular Cell Biology, 2010Co-Authors: Paul B. Talbert, Steven HenikoffAbstract:Histones wrap DNA to form nucleosome particles that compact eukaryotic genomes. Variant Histones have evolved crucial roles in chromosome segregation, transcriptional regulation, DNA repair, sperm packaging and other processes. 'Universal' histone variants emerged early in eukaryotic evolution and were later displaced for bulk packaging roles by the canonical Histones (H2A, H2B, H3 and H4), the synthesis of which is coupled to DNA replication. Further specializations of histone variants have evolved in some lineages to perform additional tasks. Differences among histone variants in their stability, DNA wrapping, specialized domains that regulate access to DNA, and post-translational modifications, underlie the diverse functions that Histones have acquired in evolution. Histone core particles are spools for wrapping DNA, whereas histone variants have evolved diverse additional roles in chromosome metabolism. Some variants mediate universal functions, such as chromosome segregation and DNA repair, and others specialize in organism-specific tasks. Canonical Histones H2A, H2B, H3 and H4 wrap DNA to form nucleosome particles that compact the genome. Histone variants have diverse additional roles in chromosome metabolism and can differ from canonical Histones in stability, DNA wrapping and specialized domains. The 'universal' variants, centromeric histone variant H3 (CenH3), H3.3, H2A.Z and H2A.X, appeared before the divergence of modern eukaryotes and function in common eukaryotic cellular processes such as histone replacement, chromosome segregation, DNA repair, and transcriptional regulation. Specialized Histones have arisen in some lineages to perform additional tasks. Centromeric nucleosomes contain CenH3 and form the essential foundation of the kinetochore. The subunit composition of the CenH3 histone core has been the subject of lively debate and it has been found to wrap DNA in a right-handed direction, opposite to that of ordinary nucleosomes. H2A.Z has a conserved role in transcription initiation that might be descended from a hypothetical ancient mode of gene regulation by histone variants found in modern trypanosomes. Dynamic cellular processes might dramatically alter the stability of H2A.Z nucleosomes and thereby facilitate transcription initiation. Chromatin must be remodelled in processes such as DNA repair and sex chromosome silencing. Variants H2A.X and H3.3 have prominent roles in remodelling, with specialized sperm Histones and protamines mediating sperm packaging and decondensation. Lineage-specific H2A variants have diverse carboxy-terminal tails that can wrap more DNA with additional oligopeptide motifs, or less DNA with a shorter docking domain. They sometimes have non-histone domains, which in macroH2As inhibit polyADP-ribosylation and contribute to conditional gene silencing.
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histone variants ancient wrap artists of the epigenome
Nature Reviews Molecular Cell Biology, 2010Co-Authors: Paul B. Talbert, Steven HenikoffAbstract:Histones wrap DNA to form nucleosome particles that compact eukaryotic genomes. Variant Histones have evolved crucial roles in chromosome segregation, transcriptional regulation, DNA repair, sperm packaging and other processes. 'Universal' histone variants emerged early in eukaryotic evolution and were later displaced for bulk packaging roles by the canonical Histones (H2A, H2B, H3 and H4), the synthesis of which is coupled to DNA replication. Further specializations of histone variants have evolved in some lineages to perform additional tasks. Differences among histone variants in their stability, DNA wrapping, specialized domains that regulate access to DNA, and post-translational modifications, underlie the diverse functions that Histones have acquired in evolution.
Anja Groth - One of the best experts on this subject based on the ideXlab platform.
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mcm2 promotes symmetric inheritance of modified Histones during dna replication
Science, 2018Co-Authors: Nataliya Petryk, Caroline B. Strømme, Anne Strandsby, Maria Dalby, Alice Wenger, Robin Andersson, Anja GrothAbstract:During genome replication, parental Histones are recycled to newly replicated DNA with their posttranslational modifications (PTMs). Whether sister chromatids inherit modified Histones evenly remains unknown. We measured histone PTM partition to sister chromatids in embryonic stem cells. We found that parental Histones H3-H4 segregate to both daughter DNA strands with a weak leading-strand bias, skewing partition at topologically associating domain (TAD) borders and enhancers proximal to replication initiation zones. Segregation of parental Histones to the leading strand increased markedly in cells with histone-binding mutations in MCM2, part of the replicative helicase, exacerbating histone PTM sister chromatid asymmetry. This work reveals how Histones are inherited to sister chromatids and identifies a mechanism by which the replication machinery ensures symmetric cell division.
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Histone chaperone networks shaping chromatin function
Nature Reviews Molecular Cell Biology, 2017Co-Authors: Colin M. Hammond, Caroline B. Strømme, Hongda Huang, Dinshaw J. Patel, Anja GrothAbstract:Histone chaperones safeguard the chromatin template and shield Histones from promiscuous interactions to ensure their proper storage, transport, post-translational modification, nucleosome assembly and turnover. The association of Histones with specific chaperone complexes is important for their folding, oligomerization, post-translational modification, nuclear import, stability, assembly and genomic localization. In this way, the chaperoning of soluble Histones is a key determinant of histone availability and fate, which affects all chromosomal processes, including gene expression, chromosome segregation and genome replication and repair. Here, we review the distinct structural and functional properties of the expanding network of histone chaperones. We emphasize how chaperones cooperate in the histone chaperone network and via co-chaperone complexes to match histone supply with demand, thereby promoting proper nucleosome assembly and maintaining epigenetic information by recycling modified Histones evicted from chromatin. Chromatin integrity and functionality is governed by the controlled assembly and disassembly of nucleosomes. An elaborate histone chaperone network governs histone provision, chromatin assembly, histone recycling and histone turnover. Histone chaperone networks operate through histone-dependent co-chaperone interactions and direct chaperone–chaperone contacts. The mode of action of histone chaperones is interpreted from structural and biochemical studies of histone–chaperone complexes. Key molecular functions of histone chaperones include the shielding of functional histone interfaces and trapping Histones in non-nucleosomal conformations. The integration of histone chaperone function across DNA metabolic processes acts to maintain genome and epigenome integrity.
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histone chaperone networks shaping chromatin function
Nature Reviews Molecular Cell Biology, 2017Co-Authors: Colin Hammond, Caroline B. Strømme, Hongda Huang, Dinshaw J. Patel, Anja GrothAbstract:The association of Histones with specific chaperone complexes is important for their folding, oligomerization, post-translational modification, nuclear import, stability, assembly and genomic localization. In this way, the chaperoning of soluble Histones is a key determinant of histone availability and fate, which affects all chromosomal processes, including gene expression, chromosome segregation and genome replication and repair. Here, we review the distinct structural and functional properties of the expanding network of histone chaperones. We emphasize how chaperones cooperate in the histone chaperone network and via co-chaperone complexes to match histone supply with demand, thereby promoting proper nucleosome assembly and maintaining epigenetic information by recycling modified Histones evicted from chromatin.
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A unique binding mode enables MCM2 to chaperone Histones H3–H4 at replication forks
Nature Structural & Molecular Biology, 2015Co-Authors: Hongda Huang, Caroline B. Strømme, Anja Groth, Giulia Saredi, Martina Hödl, Anne Strandsby, Cristina González-aguilera, Shoudeng Chen, Dinshaw J. PatelAbstract:During DNA replication, chromatin is reassembled by recycling of modified old Histones and deposition of new ones. How histone dynamics integrates with DNA replication to maintain genome and epigenome information remains unclear. Here, we reveal how human MCM2, part of the replicative helicase, chaperones Histones H3–H4. Our first structure shows an H3–H4 tetramer bound by two MCM2 histone-binding domains (HBDs), which hijack interaction sites used by nucleosomal DNA. Our second structure reveals MCM2 and ASF1 cochaperoning an H3–H4 dimer. Mutational analyses show that the MCM2 HBD is required for MCM2–7 histone-chaperone function and normal cell proliferation. Further, we show that MCM2 can chaperone both new and old canonical Histones H3–H4 as well as H3.3 and CENPA variants. The unique histone-binding mode of MCM2 thus endows the replicative helicase with ideal properties for recycling Histones genome wide during DNA replication. Chromatin reassembly after replication requires recycling of old and deposition of new Histones. Structural insights into how MCM2, part of the replicative helicase, interacts with H3–H4 suggest a function in histone recycling at replication forks.
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a unique binding mode enables mcm2 to chaperone Histones h3 h4 at replication forks
Nature Structural & Molecular Biology, 2015Co-Authors: Hongda Huang, Caroline B. Strømme, Anja Groth, Giulia Saredi, Martina Hödl, Anne Strandsby, Shoudeng Chen, Cristina Gonzalezaguilera, Dinshaw J. PatelAbstract:During DNA replication, chromatin is reassembled by recycling of modified old Histones and deposition of new ones. How histone dynamics integrates with DNA replication to maintain genome and epigenome information remains unclear. Here, we reveal how human MCM2, part of the replicative helicase, chaperones Histones H3-H4. Our first structure shows an H3-H4 tetramer bound by two MCM2 histone-binding domains (HBDs), which hijack interaction sites used by nucleosomal DNA. Our second structure reveals MCM2 and ASF1 cochaperoning an H3-H4 dimer. Mutational analyses show that the MCM2 HBD is required for MCM2-7 histone-chaperone function and normal cell proliferation. Further, we show that MCM2 can chaperone both new and old canonical Histones H3-H4 as well as H3.3 and CENPA variants. The unique histone-binding mode of MCM2 thus endows the replicative helicase with ideal properties for recycling Histones genome wide during DNA replication.
David Horn - One of the best experts on this subject based on the ideXlab platform.
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Trypanosomatid Histones: Trypanosomatid Histones
Molecular Microbiology, 2004Co-Authors: Sam Alsford, David HornAbstract:The Histones are responsible for packaging and regulating access to eukaryotic genomes. Trypanosomatids are flagellated protists that diverged early from the eukaryotic lineage and include parasites that cause disease in humans and other mammals. Here, we review the properties of Histones in parasitic trypanosomatids, from gene organization and sequence to expression, post-translational modification and function within chromatin. Phylogenetic and experimental analysis indicates that certain specifically conserved histone sequence motifs, particularly within the N-terminal 'tail' domains, possibly represent functionally important modification substrates conserved throughout the eukaryotic lineage. For example, histone H3 contains a highly conserved methylation substrate. Trypanosomatids also possess at least three variant Histones. Among these is an orthologue of H2A.Z, a histone involved in protecting 'active' chromatin from silencing in yeast. Histones provide docking platforms for a variety of regulatory factors. The presence of histone modification and variant Histones in trypanosomatids therefore represents evidence for a network that provides the discrimination required to regulate transcription, recombination, repair and chromosome replication and segregation.