DOCSLIB.ORG

Commentary the Histone Fold: Evolutionary Questions V

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Commentary the Histone Fold: Evolutionary Questions V Proc. Natl. Acad. Sci. USA Vol. 92, pp. 11328-11330, December 1995 Commentary The histone fold: Evolutionary questions V. Ramakrishnan Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84132 While histones as a class of protein asso- of each dimer pair had been suggested by central helix in the histone fold arose as a ciated with DNA have been known for NMR studies (7, 8). result of a fusion between helices from over a hundred years, our current ideas of In a recent issue of the Proceedings (9), each HSH motif. Since the basic structural how histones associate with DNA began Arents and Moudrianakis use the struc- unit is half a fold, this lends support to the with the discovery of the nucleosome as a ture of the core histones to investigate the idea of a gene-doubling in the histones, basic structural unit of chromatin (1, 2). In chemical and structural nature of the his- although it is clearly present in all the the nucleosome, two left-handed super- tone fold and offer arguments for a com- histones and not just H2A as suggested by helical turns of DNA wrap around an mon origin for the core histones. In a sequence comparison studies. Moreover, octameric histone core consisting of two related paper (10), it is shown that the this suggests that the gene-doubling event copies of each of the four core histones- histone fold occurs in a variety of different occurred before the differentiation of the H2A, H2B, H3, and H4. proteins. Taken together, these results core histones into the four types. Arents The publication by Moudrianakis and show that the fold forms the basis for a and Moudrianakis (9) have now made coworkers of the crystal structure of the distinct family of proteins. quantitative comparisons of the degree of histone octamer (3) was a landmark in the Each of the core histones is highly con- structural similarity between the histone field of chromatin. An immediate reason served (11, 12). Histones H3 and H4 are folds of the four core histones. These was that the crystal structure was in good among the most highly conserved proteins comparisons show that the fold is quite agreement with previous electron-micro- known, both in sequence and in length. similar in the four histones. If the N- scopic studies on the octamer (4), as well Histones H2A and H2B have regions that terminal and C-terminal halves of the as with the crystal structure of the nucleo- are more variable, especially at their ter- histone fold (or just the HSH motif) are some core particle at 7 A (5), thereby mini, but each has a highly conserved compared, the similarity is even greater, resolving an earlier controversy. The sur- core. However, the four core histones but this is not unexpected because the face of the octamer had a left-handed have little sequence similarity with respect motif being compared is twice as small helical ramp to which DNA presumably to one another, with pairwise identities and may have fewer degrees of freedom was bound in the nucleosome. When DNA that range from 15% to 20%. structurally. Apart from the structural was modeled onto this ramp, it agreed Despite the low sequence identity, a comparisons, other arguments are offered very well with the general features of the common origin for the core histones had for a common origin for the core histones. DNA observed in the nucleosome core been suggested by comparisons of the core Within each dimer, the fold portions of the particle (5). This showed that the structure histone amino acid sequences (13, 14). histones are related by an approximate of the isolated octamer was likely to be These studies suggested that the core hi- two-fold axis (see Fig. 1). This suggests similar to its structure in the nucleosome, stones were related to one another, but that, although today the histone dimers thus establishing the relevance of the work not to the linker histone Hi. Further, both are heterotypic, the ancestral dimer may for chromatin. studies offered evidence that histone H2A have been a homodimer with a true two- However, the crystal structure of the had an internal repeat that suggested that fold axis. More importantly, the point is octamer was important for a more funda- it was the product of a gene doubling made that histone-like proteins in archae- mental reason: it was the first structure at event. However, a study that compared bacteria are more similar to each of the sufficient resolution to allow the tertiary gene sequences questioned the gene dou- core histones than any one of the core fold of the individual core histones to be bling of H2A (15), and there were some histones is to the others. determined, with some surprising results. inconsistencies in the conclusions of the It is not difficult to rationalize why each It has been known for a long time that three studies, perhaps because of the lim- core histone has been highly conserved. histones associate with one another in ited number of complete histone se- Each histone has to make numerous in- solution. The most stable interactions are quences available at the time as well as the teractions, including interactions with its those of the heterotypic dimers H2A-H2B low degree of sequence identity. Because dimer partner, with other components of and H3-H4 (6). The H3-H4 dimers fur- ofthese inconsistencies, these studies were the octamer, and with DNA, and is there- ther associate to form a stable (H3-H4)2 not regarded as definitive [see discussion by fore subject to a variety of selective pres- tetramer. The crystal structure of the oc- van Holde (16)]. Nevertheless, gene dou- sures. However, this in itself creates an- tamer shows that the histones are indeed bling in H2A was also suggested by van other puzzle. If the core histones de- associated as heterotypic dimers within Holde (16), who showed a sequence simi- scended from a common ancestor, it is the octamer and revealed the basis for this larity between the N-terminal region of the clear that they have diverged considerably dimerization: despite little sequence sim- archaebacterial DNA-binding protein HTa over time into the four types. If they were ilarity, all four histones share a common with both the N- and C-terminal domains of allowed to diverge in this manner, what structural motif, the histone fold, which is H2A. It now turns out that the basic con- slowed the divergence once the four core involved in dimerization with its partner. clusions of these sequence comparison stud- histones had differentiated? As shown in Fig. 1 for the H3-H4 dimer, ies, although incomplete, were right. Although arguments have been made each histone is highly elongated and clasps Subsequent analysis showed that the for why the core histones have their par- its partner in the dimer by means of ex- histone fold itself could be considered as ticular structure to facilitate the formation tensive interactions in what Arents et al. a repeat of a basic helix-strand-helix of the octamer and the nucleosome (3), it (3) term a "handshake motif." Such ex- (HSH) motif that occurred in both halves is not clear that four different subtypes are tensive interactions between the members of the fold (17); this suggests that the long needed to form nucleosome-like struc- 11328 Commentary: Ramakrishnan Proc. Natl. Acad. Sci. USA 92 (1995) 11329 FIG. 1. Stereo ribbon diagram showing the involvement of the histone fold in the formation of the H3-H4 dimer present in the histone octamer (3), with the C termini of the chains marked for identification. The helix-strand-helix (HSH) motif that forms each half of the fold is present in all four core histones, and the long central helix can be considered the result of the fusion of two helices, one from each half. The H2A-H2B dimer has a similar structure. (Figure courtesy of E. N. Moudrianakis.) tures containing superhelical DNA. In of H3 or H4. Histones H2A and H2B may the family are elucidated, the diversity of bacteria, the histone-like protein HU can have been later players, whose role is roles played by the fold will become clear. supercoil DNA to form beaded structures further condensation of nucleosomal Apart from identifying evolutionary re- that are reminiscent of nucleosomes (18). DNA as well as modulation of transcrip- lationships, the structure of the octamer The three-dimensional structure of HU (19) tion, and they may have diverged as these provides the basis to answer several bio- suggests how a single protein could self- roles, especially the latter, changed over chemical questions. Each of the core his- associate and bend DNA around itself evolution. In the absence of other proteins tones has some tendency to self-associate In today's nucleosome, the roles of the that are homologous to the histones, such (6), but the specific dimers (H2A-H2B) (H3-H4)2 tetramer and the H2A-H2B evolutionary hypotheses are difficult to and H3-H4) form with higher affinity dimers are very different. The tetramer is test. Interestingly, two such proteins have than either homodimers or other hetero- thought to be the first to associate with been identified recently: the centromere- typic combinations. What is the chemical DNA; it organizes the central 120 bp of associated proteins CSE4 and CENP-A basis of this specificity? And what is the nucleosomal DNA (20) and is known to both have a high degree of homology with chemical basis for the specific stabilization determine nucleosome positioning (21).
Load more

Recommended publications
  • Topography of the Histone Octamer Surface: Repeating Structural Motifs Utilized in the Docking of Nucleosomal
    Proc. Natl. Acad. Sci. USA Vol. 90, pp. 10489-10493, November 1993 Biochemistry Topography of the histone octamer surface: Repeating structural motifs utilized in the docking of nucleosomal DNA (histone fold/helix-strand-helix motif/parallel fi bridge/binary DNA binding sites/nucleosome) GINA ARENTS* AND EVANGELOS N. MOUDRIANAKIS*t *Department of Biology, The Johns Hopkins University, Baltimore, MD 21218; and tDepartment of Biology, University of Athens, Athens, Greece Communicated by Christian B. Anfinsen, August 5, 1993 ABSTRACT The histone octamer core of the nucleosome is interactions. The model offers strong predictive criteria for a protein superhelix offour spirally arrayed histone dimers. The structural and genetic biology. cylindrical face of this superhelix is marked by intradimer and interdimer pseudodyad axes, which derive from the nature ofthe METHODS histone fold. The histone fold appears as the result of a tandem, parallel duplication of the "helix-strand-helix" motif. This The determination of the structure of the histone octamer at motif, by its occurrence in the four dimers, gives rise torepetitive 3.1 A has been described (3). The overall shape and volume structural elements-i.e., the "parallel 13 bridges" and the of this tripartite structure is in agreement with the results of "paired ends of helix I" motifs. A preponderance of positive three independent studies based on differing methodolo- charges on the surface of the octamer appears as a left-handed gies-i.e., x-ray diffraction, neutron diffraction, and electron spiral situated at the expected path of the DNA. We have microscopic image reconstruction (4-6). Furthermore, the matched a subset of DNA pseudodyads with the octamer identification of the histone fold, a tertiary structure motif of pseudodyads and thus have built a model of the nucleosome.
    [Show full text]
  • Functional Domains for Assembly of Histones H3 and H4 Into the Chromatin of Xenopus Embryos
    Proc. Natl. Acad. Sci. USA Vol. 93, pp. 12780–12785, November 1996 Biochemistry Functional domains for assembly of histones H3 and H4 into the chromatin of Xenopus embryos LITA FREEMAN,HITOSHI KURUMIZAKA, AND ALAN P. WOLFFE* Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2710 Communicated by Stuart L. Schreiber, Harvard University, Cambridge, MA, September 3, 1996 (received for review May 31, 1996) ABSTRACT Histones H3 and H4 have a well defined Modification of the N-terminal tail of H4 by acetylation has structural role in the nucleosome and an established role in been correlated with both transcription (25, 26) and nucleo- the regulation of transcription. We have made use of a some assembly (27, 28). Direct evidence for a causal role for microinjection strategy using Xenopus embryos to define the H4 acetylation in these events is, however, yet to be estab- minimal structural components of H3 and H4 necessary for lished. Tryptic removal of the N-terminal tail of histone H4 nucleosome assembly into metazoan chromosomes in vivo.We from the nucleosome or acetylation of the tail does not find that both the N-terminal tail of H4, including all sites of influence the helical periodicity of DNA in the nucleosome but acetylation, and the C-terminal a-helix of the H4 histone fold might influence the exact path taken by the double helix as it domain are dispensable for chromatin assembly. The N- wraps around the histone fold domains of the core histones (29, terminal tail and an N-terminal a-helix of H3 are also 30).
    [Show full text]
  • Recurrent Evolution of DNA-Binding Motifs in the Drosophila Centromeric Histone
    Recurrent evolution of DNA-binding motifs in the Drosophila centromeric histone Harmit S. Malik*, Danielle Vermaak*, and Steven Henikoff*†‡ †Howard Hughes Medical Institute, *Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 Communicated by Stanley M. Gartler, University of Washington, Seattle, WA, December 12, 2001 (received for review October 29, 2001) All eukaryotes contain centromere-specific histone H3 variants being one of the most evolutionarily constrained classes of (CenH3s), which replace H3 in centromeric chromatin. We have eukaryotic proteins. Second, CenH3s are evolving adaptively, previously documented the adaptive evolution of the Drosophila presumably in concert with centromeres, which consist of the CenH3 (Cid) in comparisons of Drosophila melanogaster and Dro- most rapidly evolving DNA in the genome. sophila simulans, a divergence of Ϸ2.5 million years. We have Chromosomes (and their centromeres) may compete at mei- proposed that rapidly changing centromeric DNA may be driving osis I for inclusion into the oocyte (11). A centromeric satellite CenH3’s altered DNA-binding specificity. Here, we compare Cid expansion could bias centromeric strength, leading to preferred sequences from a phylogenetically broader group of Drosophila inclusion in the oocyte, but also to increased nondisjunction. A species to suggest that Cid has been evolving adaptively for at least subsequent alteration of CenH3’s DNA-binding preferences 25 million years. Our analysis also reveals conserved blocks not could restore parity among different chromosomes (2), thereby only in the histone-fold domain but also in the N-terminal tail. In alleviating the deleterious consequences of satellite drive. Suc- several lineages, the N-terminal tail of Cid is characterized by cessive rounds of satellite and CenH3 drive are detected as an subgroup-specific oligopeptide expansions.
    [Show full text]
  • Crystal Structure of the Nucleosome Core Particle at 2.8Å Resolution Karolin Luger, Armin W
    Crystal structure of the nucleosome core particle at 2.8Å resolution Karolin Luger, Armin W. Mader, Robin K. Richmond, David R Sargent & Timothy J. Richmond Institut fur Molekularbiologie und Biophysik ETHZ, ETH-Hönggerberg, CH-8093 Zürich, Switzerland Nature, Vol 389, pages 251-260 The X-ray crystal structure of the nucleosome core particle of chromatin shows in atomic detail how the histone protein octamer is assembled and how 146 base pairs of DNA are organized into a superhelix around it. Both histone/histone and histone/DNA interactions depend on the histone fold domains and additional, well ordered structure elements extending from this motif. Histone amino-terminal tails pass over and between the gyros of the DNA superhelix to contact neighboring particles. The lack of uniformity between multiple histone/DNA-binding sites causes the DNA to deviate from ideal superhelix geometry. DNA in chromatin is organized in arrays of nucleosomes (1). Two copies of each histone protein, H2A, H2B, H3 and H4, are assembled into an octamer that has 145-147 base pairs (bp) of DNA wrapped around it to form a nucleosome core (of relative molecular mass 206K). This highly conserved nucleoprotein complex occurs essentially every 200 ± 40 bp throughout all eukaryotic genomes (2). The repeating nucleosome cores further assemble into higher-order structures which are stabilized by the linker histone H1 and these compact linear DNA overall by a factor of 30-40. The nucleosome (nucleosome core, linker DNA and H1) thereby shapes the DNA molecule both at the atomic level through DNA bending, and on the much larger scale of genes by forming higher- order helices (3).
    [Show full text]
  • Containing Protein That Replaces TAF6 in Drosophila SAGA Is Required for SAGA-Dependent Gene Expression
    Downloaded from genesdev.cshlp.org on October 2, 2021 - Published by Cold Spring Harbor Laboratory Press RESEARCH COMMUNICATION shown previously that Drosophila SAGA (dSAGA) in- A novel histone fold domain- cludes the orthologs of most components of the yeast containing protein that replaces SAGA (ySAGA) complex (Supplemental Table S1; Kusch et al. 2003; Muratoglu et al. 2003; Guelman et al. 2006; TAF6 in Drosophila SAGA is Kurshakova et al. 2007; Weake et al. 2008). In addition, required for SAGA-dependent dSAGA contains subunits that are unique to the fly com- plex, such as the WD repeat-containing protein WDA gene expression (Guelman et al. 2006). SAGA is essential for development in multicellular Vikki M. Weake,1 Selene K. Swanson,1 organisms, and Gcn5 is required for viability in both Arcady Mushegian,1,2 Laurence Florens,1 mice and Drosophila (Xu et al. 2000; Carre et al. 2005). Michael P. Washburn,1,3 Susan M. Abmayr,1,4 Furthermore, mutations that disrupt the HAT activity of and Jerry L. Workman1,5 dSAGA, such as ada2b and wda, result in lethality in flies (Qi et al. 2004; Pankotai et al. 2005; Guelman et al. 2006). 1Stowers Institute for Medical Research, Kansas City, Missouri Moreover, mutations that specifically affect the ubiquitin 64110, USA; 2Department of Microbiology, Molecular Genetics protease activity of dSAGA are lethal, and result in and Immunology, University of Kansas Medical Center, Kansas defects in axon targeting in the larval eye–brain complex City, Kansas 66160, USA; 3Department of Pathology and (Weake et al. 2008). To characterize dSAGA more fully, Laboratory Medicine, University of Kansas Medical Center, we sought to identify orthologs of all ySAGA compo- Kansas City, Kansas 66160, USA; 4Department of Anatomy and nents, as there are subunits present in the ySAGA and Cell Biology, University of Kansas Medical Center, Kansas City, human SAGA complexes for which orthologs have not Kansas 66160, USA yet been identified in flies (Rodriguez-Navarro 2009).
    [Show full text]
  • Histone Variants — Ancient Wrap Artists of the Epigenome
    REVIEWS CHROMATIN DYNAMICS Histone variants — ancient wrap artists of the epigenome Paul B. Talbert and Steven Henikoff Abstract | 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 chaperone Nearly all eukaryotes wrap their DNA around histones to In this Review, we consider the diversity and evolution of An escort protein that form nucleosomes that compact the genome while still core histone variants, from archaeal ancestors to univer- performs a transfer reaction on allowing access for active processes such as trans cription, sal eukaryotic variants to lineage-specific variants and a histone, such as deposition replication and DNA repair. Each nucleosome core variant-specific post-translational modifications (PTMs). onto DNA, eviction from DNA, transfer to another chaperone particle comprises ~ 147 bp of DNA wrapped in 1.7 turns We summarize their diverse and dynamic interactions as or enzyme, or storage for later around a protein octamer of 2 molecules of each of the 4 ‘wrap artists’ of DNA and discuss recent developments use.
    [Show full text]
  • Histone H4 and the Maintenance of Genome Integrity
    Downloaded from genesdev.cshlp.org on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press Histone H4 and the maintenance of genome integrity Paul C. Megee, 1 Brian A. Morgan, 2 and M. Mitchell Smith 3 Department of Microbiology, University of Virginia School of Medicine Charlottesville, Virginia 22908 USA The normal progression of Saccharomyces cerevisiae through nuclear division requires the function of the amino-terminal domain of histone H4. Mutations that delete the domain, or alter 4 conserved lysine residues within the domain, cause a marked delay during the G2 +M phases of the cell cycle. Site-directed mutagenesis of single and multiple lysine residues failed to map this phenotype to any particular site; the defect was only observed when all four lysines were mutated. Starting with a quadruple lysine-to-glutamine substitution allele, the insertion of a tripeptide containing a single extra lysine residue suppressed the G2+M cell cycle defect. Thus, the amino-terminal domain of histone H4 has novel genetic functions that depend on the presence of lysine per se, and not a specific primary peptide sequence. To determine the nature of this function, we examined H4 mutants that were also defective for G2/M checkpoint pathways. Disruption of the mitotic spindle checkpoint pathway had no effect on the phenotype of the histone amino-terminal domain mutant. However, disruption of RADg, which is part of the pathway that monitors DNA integrity, caused precocious progression of the H4 mutant through nuclear division and increased cell death. These results indicate that the lysine-dependent function of histone H4 is required for the maintenance of genome integrity, and that DNA damage resulting from the loss of this function activates the RAD9-dependent G2/M checkpoint pathway.
    [Show full text]
  • Commentary the Histone Fold: Evolutionary Questions V
    Proc. Natl. Acad. Sci. USA Vol. 92, pp. 11328-11330, December 1995 Commentary The histone fold: Evolutionary questions V. Ramakrishnan Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84132 While histones as a class of protein asso- of each dimer pair had been suggested by central helix in the histone fold arose as a ciated with DNA have been known for NMR studies (7, 8). result of a fusion between helices from over a hundred years, our current ideas of In a recent issue of the Proceedings (9), each HSH motif. Since the basic structural how histones associate with DNA began Arents and Moudrianakis use the struc- unit is half a fold, this lends support to the with the discovery of the nucleosome as a ture of the core histones to investigate the idea of a gene-doubling in the histones, basic structural unit of chromatin (1, 2). In chemical and structural nature of the his- although it is clearly present in all the the nucleosome, two left-handed super- tone fold and offer arguments for a com- histones and not just H2A as suggested by helical turns of DNA wrap around an mon origin for the core histones. In a sequence comparison studies. Moreover, octameric histone core consisting of two related paper (10), it is shown that the this suggests that the gene-doubling event copies of each of the four core histones- histone fold occurs in a variety of different occurred before the differentiation of the H2A, H2B, H3, and H4. proteins. Taken together, these results core histones into the four types.
    [Show full text]
  • The Histone Fold
    Proc. Natl. Acad. Sci. USA Vol. 92, pp. 11170-11174, November 1995 Biochemistry The histone fold: A ubiqu'itous architectural motif utilized in DNA compaction and protein dimerization (paired-element motif/archaeal histones/centromeric CENP-A/transcription/evolution) GINA ARENTS* AND EVANGELOS N. MOUDRIANAKIS*t *Department of Biology, The Johns Hopkins University, Baltimore, MD 21218; and tBiology Department, University of Athens, Athens, Greece Communicated by Hamilton 0. Smith, Johns Hopkins School of Medicine, Baltimore, MD, August 21, 1995 (received for review July 6, 1995) ABSTRACT The histones of all eukaryotes show only a histone fold regions of the four histone chains will be referred low degree of primary structure homology, but our earlier to as FH2A, FH2B, FH3, and FH4. All comparisons between crystallographic results defined a three-dimensional struc- histone structures were performed using the program ALIGN, tural motif, the histone fold, common to all core histones. We kindly made available to us by Mario Amzel. ALIGN calculates now examine the specific architectural patterns within the fold the best fit and rms deviation between sets of equivalent a and analyze the nature of the amino acid residues within its carbon coordinates. The histone coordinates employed in the functional segments. The histone fold emerges as a funda- calculation are taken from the 3.1-A, partially refined (R = mental protein dimerization motifwhile the differentiations of 26%), histone octamer structure (1). In performing the cal- the tips of the histone dimers appear to provide the rules of culations, allowance was made for a single-site deletion in the core octamer assembly and the basis for nucleosome regula- loop region ofH4 that follows helix I.
    [Show full text]
  • H2A Histone-Fold and DNA Elements in Nucleosome Activate SWR1
    1 2 3 4 5 H2A histone-fold and DNA elements in nucleosome 6 activate SWR1-mediated H2A.Z replacement 7 8 9 10 11 12 13 14 15 16 Anand Ranjan1,*, Feng Wang2, Gaku Mizuguchi1, Debbie Wei2, Yingzi 17 Huang2, and Carl Wu1,2,* 18 19 20 21 22 23 24 1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United 25 States 26 2Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, 27 National Institutes of Health, Bethesda, United States 28 29 *Correspondence: [email protected] (A.R.), [email protected] (C.W.) 30 Ranjan et al. 2015 31 Abstract 32 The histone variant H2A.Z is a universal mark of gene promoters, enhancers and 33 regulatory elements in eukaryotic chromatin. The chromatin remodeler SWR1 34 mediates site-specific incorporation of H2A.Z by a multi-step histone replacement 35 reaction, evicting histone H2A-H2B from the canonical nucleosome and 36 depositing the H2A.Z-H2B dimer. Binding of both substrates—the canonical 37 nucleosome and the H2A.Z-H2B dimer, is essential for activation of SWR1. We 38 found that SWR1 primarily recognizes key residues within the α2 helix in the 39 histone-fold of nucleosomal histone H2A, a region not previously known to 40 influence remodeler activity. Moreover, SWR1 interacts preferentially with 41 nucleosomal DNA at superhelix location 2 on the nucleosome face distal to its 42 linker-binding site. Our findings provide new molecular insights on recognition of 43 the canonical nucleosome by a chromatin remodeler, and have implications for 44 ATP-driven mechanisms of histone eviction and deposition.
    [Show full text]
  • Histone Variants in Archaea and the Evolution of Combinatorial Chromatin Complexity
    Histone variants in archaea and the evolution of combinatorial chromatin complexity Kathryn M. Stevensa,b, Jacob B. Swadlinga,b, Antoine Hochera,b, Corinna Bangc,d, Simonetta Gribaldoe, Ruth A. Schmitzc, and Tobias Warneckea,b,1 aMolecular Systems Group, Quantitative Biology Section, Medical Research Council London Institute of Medical Sciences, London W12 0NN, United Kingdom; bInstitute of Clinical Sciences, Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom; cInstitute for General Microbiology, University of Kiel, 24118 Kiel, Germany; dInstitute of Clinical Molecular Biology, University of Kiel, 24105 Kiel, Germany; and eDepartment of Microbiology, Unit “Evolutionary Biology of the Microbial Cell,” Institut Pasteur, 75015 Paris, France Edited by W. Ford Doolittle, Dalhousie University, Halifax, NS, Canada, and approved October 28, 2020 (received for review April 14, 2020) Nucleosomes in eukaryotes act as platforms for the dynamic inte- additional histone dimers can be taggedontothistetramertoyield gration of epigenetic information. Posttranslational modifications oligomers of increasing length that wrap correspondingly more DNA are reversibly added or removed and core histones exchanged for (3, 6–9). Almost all archaeal histones lack tails and PTMs have yet to paralogous variants, in concert with changing demands on tran- be reported. Many archaea do, however, encode multiple histone scription and genome accessibility. Histones are also common in paralogs (8, 10) that can flexibly homo- and heterodimerize in
    [Show full text]
  • Acetylation of H2AZ Lys 14 Is Associated with Genome-Wide Gene Activity in Yeast
    Downloaded from genesdev.cshlp.org on September 27, 2021 - Published by Cold Spring Harbor Laboratory Press Acetylation of H2AZ Lys 14 is associated with genome-wide gene activity in yeast Catherine B. Millar,1 Feng Xu,1 Kangling Zhang,2 and Michael Grunstein1,3 1Department of Biological Chemistry, Geffen School of Medicine and the Molecular Biology Institute, University of California, Los Angeles, California 90095, USA; 2Mass Spectrometry Facility, Department of Chemistry, University of California, Riverside, California 92521, USA Histone variants and their post-translational modifications help regulate chromosomal functions. Htz1 is an evolutionarily conserved H2A variant found at several promoters in the yeast Saccharomyces cerevisiae.In this study, we undertook a genome-wide analysis of Htz1 and its modifications in yeast. Using mass spectrometric analysis, we determined that Htz1 is acetylated at Lys 3, Lys 8, Lys 10, and Lys 14 within its N-terminal tail, with K14 being the most abundant acetylated site. ChIP and microarray analysis were then used to compare the location of Htz1-K14 acetylation to that of Htz1 genome-wide. The data presented here demonstrate that while Htz1 is associated preferentially with the promoters of repressed genes, K14 acetylation is enriched at the promoters of active genes, and requires two known histone acetyltransferases, Gcn5 and Esa1. In support of our genome-wide analysis, we found that the acetylatable lysines of Htz1 are required for its full deposition during nucleosome reassembly upon repression of PHO5. Since the majority of Htz1 acetylation is seen at active promoters, where nucleosomes are known to be disassembled, our data argue for a dynamic process in which reassembly of Htz1 is regulated by its acetylation at promoters during transcription.
    [Show full text]