Review Article
Archaea: The Final Frontier of Chromatin

https://doi.org/10.1016/j.jmb.2020.166791Get rights and content

Highlights

  • •

    All domains of life use proteins to compact and organize their genomes.

  • •

    Archaea combine bacterial and eukaryotic chromatin organization principles.

  • •

    Models of archaeal chromatin proteins and implications for higher order structures.

Abstract

The three domains of life employ various strategies to organize their genomes. Archaea utilize features similar to those found in both eukaryotic and bacterial chromatin to organize their DNA. In this review, we discuss the current state of research regarding the structure–function relationships of several archaeal chromatin proteins (histones, Alba, Cren7, and Sul7d). We address individual structures as well as inferred models for higher-order chromatin formation. Each protein introduces a unique phenotype to chromatin organization, and these structures are put into the context of in vivo and in vitro data. We close by discussing the present gaps in knowledge that are preventing further studies of the organization of archaeal chromatin, on both the organismal and domain level.

Introduction

All living things utilize scaffolding proteins to package their DNA as chromatin in order to protect their genetic code and regulate transcription. In eukaryotes, between 10 and 10,000 mega base pairs (Mbp) of DNA are packaged into a nucleus with a diameter of ~6 μm, with the metaphase chromosomes as the ultimate condensed form of the genome. The fundamental unit for this extreme level of compaction is the nucleosome, which consists of a histone octamer (composed of two copies each of histones H2A, H2B, H3, and H4) wrapping ~147 bp of DNA. Multiple nucleosomes are connected by linker DNA to form the classical “beads-on-a-string” arrangement.1, 2 Numerous chromatin architectural proteins, ATP-dependent chromatin remodellers, histone chaperones, and pioneer transcription factors work in conjunction with histones to manipulate the accessibility of nucleosomes and eukaryotic chromatin, both locally and globally, during transcription and replication.3, 4, 5 In contrast, archaea and bacteria, which do not have a nucleus, store only 0.1–10 Mbp of DNA in the nucleoid, a compacted circular plasmid in the cytosol. Bacteria utilize a plethora of small cationic proteins, called nucleoid associated proteins (or NAPs),6 to scaffold and protect their chromatin. Archaea, on the other hand, appear to combine the two strategies, and the use of NAPs and/or histones varies significantly within the domain and between species.

A unique feature of many archaea is their ability to grow in extreme conditions. Common extremophilic organisms include thermophiles (which grow at high temperatures, above 60 °C), halophiles (which grow at high salt conditions, even above 2 M), and acidophiles (which are able to grow at acidic pH). Each of these environments brings unique challenges to the task of organizing and structuring DNA. In thermophiles, proteins must allow for DNA flexibility, so as to permit transcription and replication, but they must simultaneously protect DNA from melting and heat-denaturation. In halophiles, elevated salt levels within the cell can cause denaturation of scaffolding proteins without proper sequence adaptations.7 Similarly, extremely low pH environments can induce charge-reversal in DNA molecules and cause the DNA double helix to melt, as well as dramatically alter the ability of cations to condense DNA.8 Even under these extreme conditions, archaea have found ways to maintain structured chromatin, highlighting the importance of ordering their genomes with the aid of proteins. It stands to reason that the proteins from each group of archaea may have separately evolved to handle specific environments, but no direct correlation or pattern between specific architectural protein sequences and type of extreme environment has been determined. This indicates that the choice of scaffolding protein may be somewhat stochastic and highlights the adaptability of protein sequences to accommodate unique conditions.

Here, we focus on four key proteins that are utilized by various archaea to organize their genomes: histones, Alba, Cren7, and Sul7d. We discuss available structures of the proteins and their unique interactions with DNA. We also discuss how these structures can be used to infer models of higher-order chromatin organization in archaea, as well as how these models can be interpreted in light of current in vivo and in vitro data. We close by discussing several key areas where advances are needed to further our understanding of archaeal chromatin structure and function.

Section snippets

Histones

Histones are perhaps the most widely studied chromatin architectural protein. They are defined by their ability to bind DNA through their core fold motif of three α-helices connected by short flexible loops (α1-L1-α2-L2-α3; Figure 2(A), (C)). For several decades, histones were thought to be exclusive to eukaryotes, where histones form an octamer to bind ~147 bp of DNA in the “beads on a string” arrangement.1, 2 However, the Reeve lab shifted this paradigm in 1990 when they discovered the first

Concluding Remarks and Future Perspective

One of the fundamental challenges an organism faces is the requirement to package its genome in a manner that protects DNA from damage, but also makes it available for transcription and replication without generating tangles and knots. While the organizational strategies of eukaryotes and bacteria are fairly well conserved within each domain of life, archaea employ a wide variety of DNA packaging principles across the domain. Euryarcheaota use minimalist histones to construct archaeasomes of

CRediT authorship contribution statement

Shawn P. Laursen: Conceptualization, Investigation, Writing - original draft, Writing - review & editing, Visualization. Samuel Bowerman: Conceptualization, Investigation, Writing - original draft, Writing - review & editing, Supervision, Funding acquisition. Karolin Luger: Conceptualization, Writing - original draft, Writing - review & editing, Supervision, Project administration, Funding acquisition.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

This work was funded by the Howard Hughes Medical Institute, and SB was supported by the National Institutes of General Medical Sciences of the National Institutes of Health under award number F32GM137496. The content of this article are the sole responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

References (88)

  • M.F. White et al.

    Holding it together: chromatin in the Archaea

    Trends Genet.

    (2002)
  • T. Tanaka et al.

    Crystal structure of archaeal chromatin protein Alba2-double-stranded DNA complex from Aeropyrum pernix K1

    J. Biol. Chem.

    (2012)
  • C. Jelinska et al.

    Obligate heterodimerization of the archaeal Alba2 protein with Alba1 provides a mechanism for control of DNA packaging

    Structure

    (2005)
  • L. Guo et al.

    Biochemical and structural insights into RNA binding by Ssh10b, a member of the highly conserved Sac10b protein family in Archaea

    J. Biol. Chem.

    (2014)
  • V.L. Marsh et al.

    Sir2 and the acetyltransferase, pat, regulate the archaeal chromatin protein, Alba

    J. Biol. Chem.

    (2005)
  • M. Gissot et al.

    Toxoplasma gondii Alba proteins are involved in translational control of gene expression

    J. Mol. Biol.

    (2013)
  • M. Grote et al.

    Ribosomal and DNA binding proteins of the thermoacidophilic archaebacterium Sulfolobus acidocaldarius

    Biochim. Biophys. Acta (BBA) Protein Struct. Mol. Enzymol.

    (1986)
  • J.C. Chan et al.

    Nothing is yet set in (Hi)stone: novel post-translational modifications regulating chromatin function

    Trends Biochem. Sci.

    (2020)
  • K. Luger et al.

    Crystal structure of the nucleosome core particle at 2.8 Å resolution

    Nature

    (1997)
  • A.L. Olins et al.

    Spheroid chromatin units (? Bodies)

    Science

    (1974)
  • C.M. Hammond et al.

    Histone chaperone networks shaping chromatin function

    Nature Rev. Mol. Cell Biol.

    (2017)
  • C.R. Clapier et al.

    Mechanisms of action and regulation of ATP-dependent chromatin-remodelling complexes

    Nature Rev. Mol. Cell Biol.

    (2017)
  • J. Markert et al.

    Nucleosomes meet their remodeler match

    Trends Biochem. Sci.

    (2020)
  • S.C. Dillon et al.

    Bacterial nucleoid-associated proteins, nucleoid structure and gene expression

    Nature Rev. Microbiol.

    (2010)
  • Z. Guo et al.

    The effect of pH on charge inversion and condensation of DNA

    Soft Matter

    (2016)
  • T.A. Williams et al.

    Integrative modeling of gene and genome evolution roots the archaeal tree of life

    Proc. Nat. Acad. Sci.

    (2017)
  • F. Mattiroli et al.

    Structure of histone-based chromatin in Archaea

    Science (New York, N.Y.)

    (2017)
  • K. Sandman et al.

    HMf, a DNA-binding protein isolated from the hyperthermophilic archaeon Methanothermus fervidus, is most closely related to histones

    Proc. Natl. Acad. Sci. USA

    (1990)
  • K. Sandman et al.

    Growth-phase-dependent synthesis of histones in the archaeon Methanothermus fervidus

    Proc. Natl. Acad. Sci. USA

    (1994)
  • B. Henneman et al.

    Structure and function of archaeal histones

    PLOS Genet.

    (2018)
  • S.L. Pereira et al.

    Archaeal nucleosomes

    Proc. Nat. Acad. Sci.

    (1997)
  • S. Bhattacharyya et al.

    Archaeal DNA on the histone merry-go-round

    FEBS J.

    (2018)
  • S. Bowerman, J. Wereszczynski, K. Luger, Archaeal chromatin ‘slinkies’ are inherently dynamic complexes with deflected...
  • D.E. Olins et al.

    Chromatin history: our view from the bridge

    Nature Rev. Mol. Cell Biol.

    (2003)
  • H. Imachi et al.

    Isolation of an archaeon at the prokaryote-eukaryote interface

    Nature

    (2020)
  • R.L. Fahrner et al.

    An ancestral nuclear protein assembly: Crystal structure of the Methanopyrus kandleri histone

    Protein Sci.

    (2001)
  • R. Ammar et al.

    Chromatin is an ancient innovation conserved between Archaea and Eukarya

    eLife

    (2012)
  • X. Tadeo et al.

    Structural basis for the aminoacid composition of proteins from halophilic archea

    PLOS Biol.

    (2009)
  • D.R. Musgrave et al.

    DNA binding by the archaeal histone HMf results in positive supercoiling

    Proc. Nat. Acad. Sci.

    (1991)
  • D. Musgrave et al.

    Negative constrained DNA supercoiling in archaeal nucleosomes

    Mol. Microbiol.

    (2000)
  • M. Rojec et al.

    Chromatinization of Escherichia coli with archaeal histones

    eLife

    (2019)
  • N. Nalabothula et al.

    Archaeal nucleosome positioning in vivo and in vitro is directed by primary sequence motifs

    BMC Genom.

    (2013)
  • K.M. Stevens et al.

    Histone variants in archaea and the evolution of combinatorial chromatin complexity

    Proc. Nat. Acad. Sci.

    (2020)
  • U. Günesdogan et al.

    Histone supply regulates S phase timing and cell cycle progression

    eLife

    (2014)

    • Cited by (20)

    • Histone variants in archaea – An undiscovered country

      2023, Seminars in Cell and Developmental Biology
      Citation Excerpt :

      Their deposition is not coupled to the cell cycle and occurs at specific locations, regulated by dedicated chaperones and remodellers (reviewed in [4–7]). Histone-fold proteins are also widespread in archaea [8–10] (Fig. 1f). In some species, they are relatively lowly expressed [10] and appear to behave more like transcription factors.

    • Epstein-Barr Virus Tegument Protein BKRF4 is a Histone Chaperone

      2022, Journal of Molecular Biology
      Citation Excerpt :

      These and other studies have expanded the understanding of histone chaperone functions. To date, histone chaperones have been found only in eukaryotes.13 DNA viruses are usually chromatinized with host histones by host chaperones during infection, which has implications for the regulation of the viral transcription and replication and thus the virus life cycle14–15.

    • Diving into Chromatin across Space and Time

      2021, Journal of Molecular Biology

    • Bacterial nucleoid is a riddle wrapped in a mystery inside an enigma

      2024, Journal of Bacteriology

    • On the origin of the nucleus: a hypothesis

      2023, Microbiology and Molecular Biology Reviews

    • Predictions of DNA mechanical properties at a genomic scale reveal potentially new functional roles of DNA flexibility

      2023, NAR Genomics and Bioinformatics
    View all citing articles on Scopus
    †

    Authors contributed equally to this work.

    View full text
    © 2020 Elsevier Ltd. All rights reserved.