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Review
. 2021 Jan 1;20(1):27-37.
doi: 10.1021/acs.jproteome.0c00442. Epub 2020 Oct 2.

Addressing the Possibility of a Histone-Like Code in Bacteria

Valerie J Carabetta  1
Affiliations
Review

Addressing the Possibility of a Histone-Like Code in Bacteria

Valerie J Carabetta. J Proteome Res. .

Abstract

Acetylation was initially discovered as a post-translational modification (PTM) on the unstructured, highly basic N-terminal tails of eukaryotic histones in the 1960s. Histone acetylation constitutes part of the "histone code", which regulates chromosome compaction and various DNA processes such as gene expression, recombination, and DNA replication. In bacteria, nucleoid-associated proteins (NAPs) are responsible these functions in that they organize and compact the chromosome and regulate some DNA processes. The highly conserved DNABII family of proteins are considered functional homologues of eukaryotic histones despite having no sequence or structural conservation. Within the past decade, a growing interest in Nε-lysine acetylation led to the discovery that hundreds of bacterial proteins are acetylated with diverse cellular functions, in direct contrast to the original thought that this was a rare phenomenon. Similarly, other previously undiscovered bacterial PTMs, like serine, threonine, and tyrosine phosphorylation, have also been characterized. In this review, the various PTMs that were discovered among DNABII family proteins, specifically histone-like protein (HU) orthologues, from large-scale proteomic studies are discussed. The functional significance of these modifications and the enzymes involved are also addressed. The discovery of novel PTMs on these proteins begs this question: is there a histone-like code in bacteria?

Keywords: HBsu; HU; HupA; HupB; acetylation; acetyltransferase; deacetylase; phosphorylation; post-translational modification; succinylation.

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Conflict of interest statement

The author declares no competing financial interest.

Figures

Figure 1.
Figure 1.
Comparison of DNA organization and condensation in histones and HU orthologues. (A) In the nucleus, the DNA is wrapped approximately two times around a core of histone proteins, composed of two copies of each histone (H2A, H2B, H3, and H4) or a histone variant. Histone H1 serves to hold the wrapped DNA in place and stabilize linker DNA between nucleosomes. The wrapping of DNA around histones at regular intervals condenses and further organizes the chromatin. (B) In bacteria, HU family proteins, either hetero- or homodimers, bind nonspecifically along the chromosome and introduce large bends (105° to > 180°). DNA can also wrap around an HU dimer in a right-handed orientation. These two actions help organize and condense the circular bacterial chromosome analogously to histones.
Figure 2.
Figure 2.
Evolutionary conservation of lysine acetylation of HU orthologues. HU orthologous sequences were obtained from the NCBI protein database. For some bacterial species, the HU orthologues exist as heterodimers, and the two subunits are denoted as HupA and HupB. The sequence alignment was performed using Geneious Prime, version 2020.1.1; the level of shading indicates the level of conservation, with black the best conserved. The identified acetylation sites from the acetylome studies listed in Table 1 are highlighted in red. The Actinobacteria (Mycobacterium tuberculosis, Saccharopolyspora erythraea, and Streptomyces roseosporus) contain a unique C-terminal extension that is rich in basic amino acids. The entire extension is about 110 amino acids and is not shown. Species included: Acinetobacter baumannii (Abau), Aeromonas hydrophila (Ahyd), Bacillus amyloliquefaciens (Bamy), Bacillus subtilis (Bsub), Clostridium acetobutylicum (Cace), Escherichia coli (Ecol), Francisella novicida (Fnov), Geobacillus kaustophilus (Gkau), M. tuberculosis (Mtub), Pseudomonas aeruginosa (Paer), Staphylococcus aureus (Saur), Spiroplasma eriocheiris (Seri), S. erythraea (Sery), Sulfurospirillum halorespirans (Shal), S. roseosporus (Sros), Synechococcus sp. (Syn), Thermus thermophilus (Tthe), Vibrio alginolyticus (Valg), Vibrio cholerae (Vcho), and Vibrio parahemolyticus (Vpar).
Figure 3.
Figure 3.
Structural location of PTMs on HU orthologues. Computational models of (A) E. coli HupA–HupB heterodimer, (B) V. alginolyticus HupA–HupB heterodimer, (C) S. eriocheiris HupA homodimer, and (D) B. subtilis HBsu homodimer are shown. For the heterodimers depicted in (A) and (B), the HupA subunit is colored green, and the HupB subunit is colored tan. Both monomers of the homodimers are depicted in (C) and (D). Acetylated residues are shown as red sticks, and phosphorylated residues are shown as yellow sticks; succinylated residues that do not overlap with an acetylation site are shown as pink sticks. The comparative models were generated using Phyre2. The Anabaena HU–DNA cocrystal structure (Protein Data Bank code 1P71) was used as the modeling template. Molecular graphics were produced with PyMOL.
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