Natural History of the Eukaryotic Chromatin Protein Methylation System

Aravind, L.; Abhiman, Saraswathi; Iyer, Lakshminarayan M.

doi:10.1016/b978-0-12-387685-0.00004-4

Cited by 65 publications

(95 citation statements)

References 260 publications

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“…Based on molecular evolutionary analysis, Aravind et al (50) proposed that eukaryotic histone methylation systems might originate in bacteria, where these enzymes are utilized for synthesis of secondary metabolites, such as antibiotics and toxins. All lysine demethylase KDM1 genes are also found to share a common single origin from a bacterial amine oxidase AOD gene (51).…”

Section: Discussionmentioning

confidence: 99%

A Prototypic Lysine Methyltransferase 4 from Archaea with Degenerate Sequence Specificity Methylates Chromatin Proteins Sul7d and Cren7 in Different Patterns

Niu

Xia

Wang

et al. 2013

Journal of Biological Chemistry

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Background:The origin of eukaryotic histone modification enzymes still remains obscure. Results: Prototypic KMT4/Dot1 from Archaea targets chromatin proteins (Sul7d and Cren7) and shows increased activity on Sul7d, but not Cren7, in the presence of DNA. Conclusion: Promiscuous aKMT4 could be regulated by chromatin environment. Significance: This study supports the prokaryotic origin model of eukaryotic histone methyltransferases and sheds light on chromatin dynamics in Archaea.

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Section: Discussionmentioning

confidence: 99%

A Prototypic Lysine Methyltransferase 4 from Archaea with Degenerate Sequence Specificity Methylates Chromatin Proteins Sul7d and Cren7 in Different Patterns

Niu

Xia

Wang

et al. 2013

Journal of Biological Chemistry

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“…[1][2][3][4] For example, the origin of several eukaryotic enzymes that add or remove a methyl group on lysines and arginines in histones and other proteins can be directly traced to bacterial pathways involved in synthesizing peptide-derived antibiotics and siderophores. 5 A 2-oxoglutarate-dependent dioxygenase derived from similar bacterial systems has also spawned the wybutosine hydroxylase/ peroxidase, an enzyme that introduces a key modification in eukaryotic tRNAPhe. 6 In a similar vein, multiple components of the peptide ligation and deubiquitination pathways in the eukaryotic ubiquitin system show evolutionary relationships with enzymes involved in diverse bacterial biosynthetic systems for cofactors (thiamine and molybdopterin), siderophores, antibiotics and the amino acid cysteine.…”

Section: Introductionmentioning

confidence: 99%

Identification of novel components of NAD-utilizing metabolic pathways and prediction of their biochemical functions

Souza

Aravind

2012

Mol. BioSyst.

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Nicotinamide adenine dinucleotide (NAD) is a ubiquitous cofactor participating in numerous redox reactions. It is also a substrate for regulatory modifications of proteins and nucleic acids via the addition of ADP-ribose moieties or removal of acyl groups by transfer to ADP-ribose. In this study, we use in-depth sequence, structure and genomic context analysis to uncover new enzymes and substrate-binding proteins in NAD-utilizing metabolic and macromolecular modification systems. We predict that Escherichia coli YbiA and related families of domains from diverse bacteria, eukaryotes, large DNA viruses and single strand RNA viruses are previously unrecognized components of NAD-utilizing pathways that probably operate on ADP-ribose derivatives. Using contextual analysis we show that some of these proteins potentially act in RNA repair, where NAD is used to remove 2 0 -3 0 cyclic phosphodiester linkages. Likewise, we predict that another family of YbiA-related enzymes is likely to comprise a novel NAD-dependent ADP-ribosylation system for proteins, in conjunction with a previously unrecognized ADP-ribosyltransferase. A similar ADP-ribosyltransferase is also coupled with MACRO or ADP-ribosylglycohydrolase domain proteins in other related systems, suggesting that all these novel systems are likely to comprise pairs of ADP-ribosylation and ribosylglycohydrolase enzymes analogous to the DraG-DraT system, and a novel group of bacterial polymorphic toxins. We present evidence that some of these coupled ADP-ribosyltransferases/ribosylglycohydrolases are likely to regulate certain restriction modification enzymes in bacteria. The ADP-ribosyltransferases found in these, the bacterial polymorphic toxin and host-directed toxin systems of bacteria such as Waddlia also throw light on the evolution of this fold and the origin of eukaryotic polyADP-ribosyltransferases and NEURL4-like ARTs, which might be involved in centrosomal assembly. We also infer a novel biosynthetic pathway that might be involved in the synthesis of a nicotinate-derived compound in conjunction with an asparagine synthetase and AMPylating peptide ligase. We use the data derived from this analysis to understand the origin and early evolutionary trajectories of key NAD-utilizing enzymes and present targets for future biochemical investigations.

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“…Our observations confirming that PbZfp KO parasites completely lacked H3K4, H3K27, and H3K36 trimethylation led us to hypothesize that the KO parasites would exhibit reduced susceptibility to DNA-damaging agents. To test our hypothesis, we exposed WT, KO, and Trunc parasites for 6 h to various concentrations (0.05%, 0.005%, and 0.0005%) of the DNA-damaging agent MMS using conditions similar to those used in our previous studies with P. falciparum (35) followed by Comet assay analysis (18). There was an MMS dose-dependent increase in Olive tail moment (OTM) values for WT, KO, and Trunc parasites (Fig.…”

Section: C2h2 Zinc Finger Protein In Malaria Transmissionmentioning

confidence: 89%

“…To quantify the percentage of damage in the parasites exposed to MMS, we counted the total number of cells, the total number of intact nuclei, and the total number of Comets for each sample and then calculated the percentage of damaged cells (18). As seen in the bottom panel in Fig.…”

Section: C2h2 Zinc Finger Protein In Malaria Transmissionmentioning

confidence: 99%

“…The PRDM9 protein contains a C-terminal module comprised of multiple C 2 H 2 -type zinc fingers (ZnF) which binds the degenerate 13-bp motif that was previously found to be associated with~40% of human hotspots, formation of doublestrand breaks (DSB), and recruitment of the recombination machinery leading to exchange of chromosomal material and DNA repair. Additionally, the ZnF domain (Zfd) in PRDM9 is fused to a SET domain which catalyzes the trimethylation of histone 3 lysine 4 (H3K4) and histone 3 lysine 36 (H3K36) associated with the hotspots (18,19). The SET domain initially characterized in Drosophila is an evolutionarily well-conserved domain associated with many chromosomal proteins and with proteins necessary for histone lysine trimethylation in mammalian cells (20).…”

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confidence: 99%

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Multifunctional Involvement of a C2H2 Zinc Finger Protein (PbZfp) in Malaria Transmission, Histone Modification, and Susceptibility to DNA Damage Response

Gopalakrishnan

Aly

Aravind

et al. 2017

mBio

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In sexually reproducing organisms, meiosis is an essential step responsible for generation of haploid gametes from diploid somatic cells. The quest for understanding regulatory mechanisms of meiotic recombination in Plasmodium led to identification of a gene encoding a protein that contains 11 copies of C 2 H 2 zinc fingers (ZnF). Reverse genetic approaches were used to create Plasmodium berghei parasites either lacking expression of full-length Plasmodium berghei zinc finger protein (PbZfp) (knockout [KO]) or expressing PbZfp lacking C-terminal zinc finger region (truncated [Trunc]). Mice infected with KO parasites survived two times longer (P Ͻ 0.0001) than mice infected with wild-type (WT) parasites. In mosquito transmission experiments, the infectivity of KO and Trunc parasites was severely compromised (Ͼ95% oocyst reduction). KO parasites revealed a total lack of trimethylation of histone 3 at several lysine residues (K4, K27, and K36) without any effect on acetylation patterns (H3K9, H3K14, and H4K16). Reduced DNA damage and reduced expression of topoisomerase-like Spo11 in the KO parasites with normal Rad51 expression further suggest a functional role for PbZfp during genetic recombination that involves DNA double-strand break (DSB) formation followed by DNA repair. These finding raise the possibility of some convergent similarities of PbZfp functions to functions of mammalian PRDM9, also a C 2 H 2 ZnF protein with histone 3 lysine 4 (H3K4) methyltransferase activity. These functions include the major role played by the latter in binding recombination hotspots in the genome during meiosis and trimethylation of the associated histones and subsequent chromatin recruitment of topoisomerase-like Spo11 to catalyze DNA DSB formation and DMC1/Rad51-mediated DNA repair and homologous recombination.IMPORTANCE Malaria parasites are haploid throughout their life cycle except for a brief time period when zygotes are produced as a result of fertilization between male and female gametes during transmission through the mosquito vector. The reciprocal recombination events that follow zygote formation ensure orderly segregation of homologous chromosomes during meiosis, creating genetic diversity among offspring. Studies presented in the current manuscript identify a novel C2H2 ZnFcontaining protein exhibiting multifunctional roles in parasite virulence, mosquito transmission, and homologous recombination during meiosis. Understanding the transmission biology of malaria will result in the identification of novel targets for transmission-blocking intervention approaches.

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Natural History of the Eukaryotic Chromatin Protein Methylation System

Cited by 65 publications

References 260 publications

A Prototypic Lysine Methyltransferase 4 from Archaea with Degenerate Sequence Specificity Methylates Chromatin Proteins Sul7d and Cren7 in Different Patterns

A Prototypic Lysine Methyltransferase 4 from Archaea with Degenerate Sequence Specificity Methylates Chromatin Proteins Sul7d and Cren7 in Different Patterns

Identification of novel components of NAD-utilizing metabolic pathways and prediction of their biochemical functions

Multifunctional Involvement of a C2H2 Zinc Finger Protein (PbZfp) in Malaria Transmission, Histone Modification, and Susceptibility to DNA Damage Response

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