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Genes, Volume 8, Issue 8 (August 2017)

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Cover Story Salinity is a major abiotic stress, reducing crop production worldwide. To cope with this, plant [...] Read more.
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Research

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Open AccessArticle Genome-Wide Analysis Reveals Extensive Changes in LncRNAs during Skeletal Muscle Development in Hu Sheep
Genes 2017, 8(8), 191; doi:10.3390/genes8080191
Received: 13 June 2017 / Revised: 21 July 2017 / Accepted: 24 July 2017 / Published: 1 August 2017
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Abstract
As an important type of noncoding RNA molecules, long non-coding RNAs (lncRNAs) act as versatile players in various biological processes. However, little is known about lncRNA regulators during sheep muscle growth. To explore functional lncRNAs during sheep muscle growth, we systematically investigated lncRNAs
[...] Read more.
As an important type of noncoding RNA molecules, long non-coding RNAs (lncRNAs) act as versatile players in various biological processes. However, little is known about lncRNA regulators during sheep muscle growth. To explore functional lncRNAs during sheep muscle growth, we systematically investigated lncRNAs using strand-specific Ribo-Zero RNA sequencing at three key developmental stages in Hu sheep. A total of 6924 lncRNAs were obtained, and the differentially expressed lncRNAs and genes were screened from (control vs. experiment) fetus vs. lamb, lamb vs. adult, and fetus vs. adult comparisons, respectively. The quantitative real-time polymerase chain reaction (qRT-PCR) analysis results correlated well with the sequencing data. Moreover, functional annotation analysis based on the Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases showed that the target genes of the differentially expressed lncRNAs were significantly enriched in organ morphogenesis, skeletal system development as well as response to stimulus and some other terms related to muscle. Furthermore, a co-expression network of the differentially expressed target genes and lncRNAs was constructed and well-known muscle growth regulators such as retrotransposon-like 1 and Junctophilin-2 were included. Finally, we investigated the expression profiles of seven lncRNAs and their target genes, and found that they played vital roles in muscle growth. This study extends the sheep muscle lncRNA database and provides novel candidate regulators for future genetic and molecular studies on sheep muscle growth, which is helpful for optimizing the production of mutton. Full article
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Open AccessArticle Characterization and Expression Profiling of Camellia sinensis Cinnamate 4-hydroxylase Genes in Phenylpropanoid Pathways
Genes 2017, 8(8), 193; doi:10.3390/genes8080193
Received: 27 June 2017 / Revised: 23 July 2017 / Accepted: 25 July 2017 / Published: 1 August 2017
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Abstract
Cinnamate 4-hydroxylase (C4H), a cytochrome P450-dependent monooxygenase, participates in the synthesis of numerous polyphenoid compounds, such as flavonoids and lignins. However, the C4H gene number and function in tea plants are not clear. We screened all available transcriptome and genome databases of tea
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Cinnamate 4-hydroxylase (C4H), a cytochrome P450-dependent monooxygenase, participates in the synthesis of numerous polyphenoid compounds, such as flavonoids and lignins. However, the C4H gene number and function in tea plants are not clear. We screened all available transcriptome and genome databases of tea plants and three C4H genes were identified and named CsC4Ha, CsC4Hb, and CsC4Hc, respectively. Both CsC4Ha and CsC4Hb have 1518-bp open reading frames that encode 505-amino acid proteins. CsC4Hc has a 1635-bp open reading frame that encodes a 544-amino acid protein. Enzymatic analysis of recombinant proteins expressed in yeast showed that the three enzymes catalyzed the formation of p-coumaric acid (4-hydroxy trans-cinnamic acid) from trans-cinnamic acid. Quantitative real-time PCR (qRT-PCR) analysis showed that CsC4Ha was highly expressed in the 4th leaf, CsC4Hb was highly expressed in tender leaves, while CsC4Hc was highly expressed in the young stems. The three CsC4Hs were induced with varying degrees by abiotic stress treatments. These results suggest they may have different subcellular localization and different physiological functions. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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Open AccessArticle Distribution of FMR1 and FMR2 Repeats in Argentinean Patients with Primary Ovarian Insufficiency
Genes 2017, 8(8), 194; doi:10.3390/genes8080194
Received: 21 May 2017 / Revised: 19 July 2017 / Accepted: 26 July 2017 / Published: 16 August 2017
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Abstract
The premutation state of FMR1 (Fragile X Mental Retardation 1) has been associated with primary ovarian insufficiency (POI), and is the most common known genetic cause for 46,XX patients. Nevertheless, very few studies have analyzed its frequency in Latin American populations. Additionally, a
[...] Read more.
The premutation state of FMR1 (Fragile X Mental Retardation 1) has been associated with primary ovarian insufficiency (POI), and is the most common known genetic cause for 46,XX patients. Nevertheless, very few studies have analyzed its frequency in Latin American populations. Additionally, a relationship between alleles carrying a cryptic microdeletion in the 5’UTR of FMR2 and the onset of POI has only been studied in one population. Our aim was to analyze the incidence of FMR1 premutations and putative microdeletions in exon 1 of FMR2 in a cohort of Argentinean women with POI. We studied 133 patients and 84 controls. Fluorescent PCR was performed, and the FMR2 exon 1 was further sequenced in samples presenting less than 11 repeats. We found the frequency of FMR1 premutations to be 6.7% and 2.9% for familial and sporadic patients, respectively. Among controls, 1/84 women presented a premutation. In addition, although we did not find microdeletions in FMR2, we observed a change (T >C) adjacent to the repeats in two sisters with POI. Given the repetitive nature of the sequence involved, we could not ascertain whether this represents a single nucleotide polymorphism (SNP) or a deletion. Therefore, a relationship between FMR2 and POI could not be established for our population. Full article
(This article belongs to the Section Human Genetics and Genomics)
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Open AccessArticle Dissecting Tissue-Specific Transcriptomic Responses from Leaf and Roots under Salt Stress in Petunia hybrida Mitchell
Genes 2017, 8(8), 195; doi:10.3390/genes8080195
Received: 9 April 2017 / Revised: 1 July 2017 / Accepted: 27 July 2017 / Published: 3 August 2017
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Abstract
One of the primary objectives of plant biotechnology is to increase resistance to abiotic stresses, such as salinity. Salinity is a major abiotic stress and increasing crop resistant to salt continues to the present day as a major challenge. Salt stress disturbs cellular
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One of the primary objectives of plant biotechnology is to increase resistance to abiotic stresses, such as salinity. Salinity is a major abiotic stress and increasing crop resistant to salt continues to the present day as a major challenge. Salt stress disturbs cellular environment leading to protein misfolding, affecting normal plant growth and causing agricultural losses worldwide. The advent of state-of-the-art technologies such as high throughput mRNA sequencing (RNA-seq) has revolutionized whole-transcriptome analysis by allowing, with high precision, to measure changes in gene expression. In this work, we used tissue-specific RNA-seq to gain insight into the Petunia hybrida transcriptional responses under NaCl stress using a controlled hydroponic system. Roots and leaves samples were taken from a continuum of 48 h of acute 150 mM NaCl. This analysis revealed a set of tissue and time point specific differentially expressed genes, such as genes related to transport, signal transduction, ion homeostasis as well as novel and undescribed genes, such as Peaxi162Scf00003g04130 and Peaxi162Scf00589g00323 expressed only in roots under salt stress. In this work, we identified early and late expressed genes in response to salt stress while providing a core of differentially express genes across all time points and tissues, including the trehalose-6-phosphate synthase 1 (TPS1), a glycosyltransferase reported in salt tolerance in other species. To test the function of the novel petunia TPS1 allele, we cloned and showed that TPS1 is a functional plant gene capable of complementing the trehalose biosynthesis pathway in a yeast tps1 mutant. The list of candidate genes to enhance salt tolerance provided in this work constitutes a major effort to better understand the detrimental effects of salinity in petunia with direct implications for other economically important Solanaceous species. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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Open AccessArticle Analysis of Argonaute 4-Associated Long Non-Coding RNA in Arabidopsis thaliana Sheds Novel Insights into Gene Regulation through RNA-Directed DNA Methylation
Genes 2017, 8(8), 198; doi:10.3390/genes8080198
Received: 22 June 2017 / Revised: 1 August 2017 / Accepted: 2 August 2017 / Published: 7 August 2017
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Abstract
RNA-directed DNA methylation (RdDM) is a plant-specific de novo DNA methylation mechanism that requires long noncoding RNA (lncRNA) as scaffold to define target genomic loci. While the role of RdDM in maintaining genome stability is well established, how it regulates protein-coding genes remains
[...] Read more.
RNA-directed DNA methylation (RdDM) is a plant-specific de novo DNA methylation mechanism that requires long noncoding RNA (lncRNA) as scaffold to define target genomic loci. While the role of RdDM in maintaining genome stability is well established, how it regulates protein-coding genes remains poorly understood and few RdDM target genes have been identified. In this study, we obtained sequences of RdDM-associated lncRNAs using nuclear RNA immunoprecipitation against ARGONAUTE 4 (AGO4), a key component of RdDM that binds specifically with the lncRNA. Comparison of these lncRNAs with gene expression data of RdDM mutants identified novel RdDM target genes. Surprisingly, a large proportion of these target genes were repressed in RdDM mutants suggesting that they are normally activated by RdDM. These RdDM-activated genes are more enriched for gene body lncRNA than the RdDM-repressed genes. Histone modification and RNA analyses of several RdDM-activated stress response genes detected increased levels of active histone mark and short RNA transcript in the lncRNA-overlapping gene body regions in the ago4 mutant despite the repressed expression of these genes. These results suggest that RdDM, or AGO4, may play a role in maintaining or activating stress response gene expression by directing gene body chromatin modification preventing cryptic transcription. Full article
(This article belongs to the Special Issue RNA Modification)
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Open AccessArticle Two C3H Type Zinc Finger Protein Genes, CpCZF1 and CpCZF2, from Chimonanthus praecox Affect Stamen Development in Arabidopsis
Genes 2017, 8(8), 199; doi:10.3390/genes8080199
Received: 3 June 2017 / Revised: 24 July 2017 / Accepted: 7 August 2017 / Published: 10 August 2017
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Abstract
Wintersweet (Chimonanthus praecox) is a popular garden plant because of its flowering time, sweet fragrance, and ornamental value. However, research into the molecular mechanism that regulates flower development in wintersweet is still limited. In this study, we sought to investigate the
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Wintersweet (Chimonanthus praecox) is a popular garden plant because of its flowering time, sweet fragrance, and ornamental value. However, research into the molecular mechanism that regulates flower development in wintersweet is still limited. In this study, we sought to investigate the molecular characteristics, expression patterns, and potential functions of two C3H-type zinc finger (CZF) protein genes, CpCZF1 and CpCZF2, which were isolated from the wintersweet flowers based on the flower developmental transcriptome database. CpCZF1 and CpCZF2 were more highly expressed in flower organs than in vegetative tissues, and during the flower development, their expression profiles were associated with flower primordial differentiation, especially that of petal and stamen primordial differentiation. Overexpression of either CpCZF1 or CpCZF2 caused alterations on stamens in transgenic Arabidopsis. The expression levels of the stamen identity-related genes, such as AGAMOUS (AG), PISTILLATA (PI), SEPALLATA1 (SEP1), SEPALLATA2 (SEP2), SEPALLATA3 (SEP3), APETALA1 (AP1), APETALA2 (AP2), and boundary gene RABBIT EAR (RBE) were significantly up-regulated in CpCZF1 overexpression lines. Additionally, the transcripts of AG, PI, APETALA3 SEP1-3, AP1, and RBE were markedly increased in CpCZF2 overexpressed plant inflorescences. Moreover, CpCZF1 and CpCZF2 could interact with each other by using yeast two-hybrid and bimolecular fluorescence complementation assays. Our results suggest that CpCZF1 and CpCZF2 may be involved in the regulation of stamen development and cause the formation of abnormal flowers in transgenic Arabidopsis plants. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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Open AccessArticle Large Introns of 5 to 10 Kilo Base Pairs Can Be Spliced out in Arabidopsis
Genes 2017, 8(8), 200; doi:10.3390/genes8080200
Received: 7 July 2017 / Revised: 4 August 2017 / Accepted: 7 August 2017 / Published: 11 August 2017
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Abstract
Most of the eukaryotic genes contain introns, which are removed from the pre-RNA during RNA processing. In contrast to the introns in animals, which are usually several kilo base pairs (kb), those in plants generally are very small, which are mostly from dozens
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Most of the eukaryotic genes contain introns, which are removed from the pre-RNA during RNA processing. In contrast to the introns in animals, which are usually several kilo base pairs (kb), those in plants generally are very small, which are mostly from dozens of base pairs (bp) to a few hundred bp. According to annotation version 10.0 of the genome of Arabidopsis thaliana, there are 127,854 introns in the nuclear genes; 99.23% of them are less than 1 kb, and only 16 introns are annotated to be larger than 5 kb, which are extremely large introns (ELI) in Arabidopsis. To learn whether these introns are true introns or not and how large introns could be in Arabidopsis, RT-PCR analysis of genes containing these ELIs were carried out. The results indicated that some of these putative introns are indeed ELIs. These ELIs are mainly composed of transposons or transposable elements (TE), excepting one, whose counterparts are also very long in diverse plant species. Thus, this study confirms the existence of introns larger than 5 kb or even 10 kb in Arabidopsis. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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Open AccessArticle Mutation Clusters from Cancer Exome
Genes 2017, 8(8), 201; doi:10.3390/genes8080201
Received: 19 June 2017 / Revised: 26 July 2017 / Accepted: 7 August 2017 / Published: 15 August 2017
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Abstract
We apply our statistically deterministic machine learning/clustering algorithm *K-means (recently developed in https://ssrn.com/abstract=2908286) to 10,656 published exome samples for 32 cancer types. A majority of cancer types exhibit a mutation clustering structure. Our results are in-sample stable. They are also out-of-sample stable
[...] Read more.
We apply our statistically deterministic machine learning/clustering algorithm *K-means (recently developed in https://ssrn.com/abstract=2908286) to 10,656 published exome samples for 32 cancer types. A majority of cancer types exhibit a mutation clustering structure. Our results are in-sample stable. They are also out-of-sample stable when applied to 1389 published genome samples across 14 cancer types. In contrast, we find in- and out-of-sample instabilities in cancer signatures extracted from exome samples via nonnegative matrix factorization (NMF), a computationally-costly and non-deterministic method. Extracting stable mutation structures from exome data could have important implications for speed and cost, which are critical for early-stage cancer diagnostics, such as novel blood-test methods currently in development. Full article
(This article belongs to the Special Issue Integrative Genomics and Systems Medicine in Cancer)
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Open AccessArticle Transcriptome Analysis Reveals Long Intergenic Noncoding RNAs Contributed to Growth and Meat Quality Differences between Yorkshire and Wannanhua Pig
Genes 2017, 8(8), 203; doi:10.3390/genes8080203 (registering DOI)
Received: 24 July 2017 / Revised: 12 August 2017 / Accepted: 14 August 2017 / Published: 18 August 2017
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Abstract
There are major differences between Yorkshire (lean-type) and Wannanhua pig (fat-type) in terms of growth performance and meat quality. Long intergenic noncoding RNAs (lincRNAs) are a class of regulators that are involved in numerous biological processes and widely identified in many species. However,
[...] Read more.
There are major differences between Yorkshire (lean-type) and Wannanhua pig (fat-type) in terms of growth performance and meat quality. Long intergenic noncoding RNAs (lincRNAs) are a class of regulators that are involved in numerous biological processes and widely identified in many species. However, the role of lincRNAs in pig is largely unknown, and the mechanisms by which they affect growth and meat quality are elusive. In this study, we used published data to identify 759 lincRNAs in porcine longissimus dorsi muscle. These putative lincRNAs shared many features with mammalian lincRNAs, such as shorter length and fewer exons. Gene ontology and pathway analysis indicated that many potential target genes (PTGs) of lincRNAs were involved in muscle growth-related and meat quality-related biological processes. Moreover, we constructed a co-expression network between differentially expressed lincRNAs (DELs) and their PTGs, and found a potential mechanism that most DELs can use to upregulate their PTGs, which may finally contribute to the growth and meat quality differences between the two breeds through an unknown manner. This work details some lincRNAs and their PTGs related to muscle growth or meat quality, and facilitates future research on the roles of lincRNAs in these two types of pig, as well as molecular-assisted breeding for pig. Full article
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Open AccessArticle Variation in the Ovine KAP6-3 Gene (KRTAP6-3) Is Associated with Variation in Mean Fibre Diameter-Associated Wool Traits
Genes 2017, 8(8), 204; doi:10.3390/genes8080204 (registering DOI)
Received: 4 July 2017 / Revised: 6 August 2017 / Accepted: 17 August 2017 / Published: 18 August 2017
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Abstract
Polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) analysis was used to investigate variation in the ovine KAP6-3 gene (KRTAP6-3) in 383 Merino × Southdown-cross lambs from four sire-lines, and to determine whether this variation affects wool traits. Five PCR-SSCP banding patterns,
[...] Read more.
Polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) analysis was used to investigate variation in the ovine KAP6-3 gene (KRTAP6-3) in 383 Merino × Southdown-cross lambs from four sire-lines, and to determine whether this variation affects wool traits. Five PCR-SSCP banding patterns, representing five different nucleotide sequences, were detected, including four previously identified (named A, B, C, and F) variants and one newly identified (named G) variant. A new non-synonymous single nucleotide polymorphism (SNP) and a 45-bp deletion were detected in variant G. Of the three common genotypes (AA, AB, and AG) identified in these sheep, wool from sheep that were AG, on average, had a lower mean fibre diameter (MFD), fibre diameter standard deviation (FDSD), and prickle factor (PF) than wool from AA sheep, whereas wool from AB sheep, on average, had a higher MFD, FDSD, and PF than wool from AA sheep. This suggests that variation in ovine KRTAP6-3 affect MFD, FDSD, and PF, and that this gene may have potential for use as a gene-maker for improving fibre diameter-associated wool traits. Full article
(This article belongs to the Section Molecular Genetics)
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Open AccessArticle Mapping of QTLs for Seed Phorbol Esters, a Toxic Chemical in Jatropha curcas (L.)
Genes 2017, 8(8), 205; doi:10.3390/genes8080205 (registering DOI)
Received: 5 July 2017 / Revised: 12 August 2017 / Accepted: 17 August 2017 / Published: 18 August 2017
Abstract
Jatropha (Jatropha curcas L.) is an oil-bearing plant that has potential to be cultivated as a biodiesel crop. The seed cake after oil extraction has 40–50% protein that can be used in animal feeds. A major limitation in utilizing the cake is
[...] Read more.
Jatropha (Jatropha curcas L.) is an oil-bearing plant that has potential to be cultivated as a biodiesel crop. The seed cake after oil extraction has 40–50% protein that can be used in animal feeds. A major limitation in utilizing the cake is the presence of phorbol esters (PE), a heat-tolerant toxic chemical. To identify the quantitative trait loci (QTLs) for PE, we constructed a genetic linkage map from an F2 population of 95 individuals from a cross “Chai Nat” × “M10” using 143 simple sequence repeat (SSR) markers. M10 is low in seed PE while Chai Nat is high. Seeds from each F2 individual were quantified for PE content by high performance liquid chromatography. A single marker analysis revealed five markers from linkage group 3 (LG3) and nine markers from LG8 associated with seed PE. Inclusive composite interval mapping identified two QTLs, each on LG3 (qPE3.1) and LG8 (qPE8.1) responsible for the PE. qPE3.1 and qPE8.1 accounted for 14.10%, and 15.49% of total variation in seed PE, respectively. Alelle(s) from M10 at qPE3.1 increased seed PE, while at qPE8.1 decreased seed PE. qPE3.1 is a new loci for PE, while qPE8.1 is the same locus with that reported recently for PE. Full article
(This article belongs to the Special Issue Plant Genomics and Epigenomics for Trait Improvement)

Review

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Open AccessReview Proteins Recognizing DNA: Structural Uniqueness and Versatility of DNA-Binding Domains in Stem Cell Transcription Factors
Genes 2017, 8(8), 192; doi:10.3390/genes8080192
Received: 10 May 2017 / Revised: 22 July 2017 / Accepted: 25 July 2017 / Published: 1 August 2017
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Abstract
Proteins in the form of transcription factors (TFs) bind to specific DNA sites that regulate cell growth, differentiation, and cell development. The interactions between proteins and DNA are important toward maintaining and expressing genetic information. Without knowing TFs structures and DNA-binding properties, it
[...] Read more.
Proteins in the form of transcription factors (TFs) bind to specific DNA sites that regulate cell growth, differentiation, and cell development. The interactions between proteins and DNA are important toward maintaining and expressing genetic information. Without knowing TFs structures and DNA-binding properties, it is difficult to completely understand the mechanisms by which genetic information is transferred between DNA and proteins. The increasing availability of structural data on protein-DNA complexes and recognition mechanisms provides deeper insights into the nature of protein-DNA interactions and therefore, allows their manipulation. TFs utilize different mechanisms to recognize their cognate DNA (direct and indirect readouts). In this review, we focus on these recognition mechanisms as well as on the analysis of the DNA-binding domains of stem cell TFs, discussing the relative role of various amino acids toward facilitating such interactions. Unveiling such mechanisms will improve our understanding of the molecular pathways through which TFs are involved in repressing and activating gene expression. Full article
(This article belongs to the Special Issue Protein-DNA Interactions)
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Open AccessReview Acetylation- and Methylation-Related Epigenetic Proteins in the Context of Their Targets
Genes 2017, 8(8), 196; doi:10.3390/genes8080196
Received: 9 May 2017 / Revised: 19 July 2017 / Accepted: 31 July 2017 / Published: 7 August 2017
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Abstract
The nucleosome surface is covered with multiple modifications that are perpetuated by eight different classes of enzymes. These enzymes modify specific target sites both on DNA and histone proteins, and these modifications have been well identified and termed “epigenetics”. These modifications play critical
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The nucleosome surface is covered with multiple modifications that are perpetuated by eight different classes of enzymes. These enzymes modify specific target sites both on DNA and histone proteins, and these modifications have been well identified and termed “epigenetics”. These modifications play critical roles, either by affecting non-histone protein recruitment to chromatin or by disturbing chromatin contacts. Their presence dictates the condensed packaging of DNA and can coordinate the orderly recruitment of various enzyme complexes for DNA manipulation. This genetic modification machinery involves various writers, readers, and erasers that have unique structures, functions, and modes of action. Regarding human disease, studies have mainly focused on the genetic mechanisms; however, alteration in the balance of epigenetic networks can result in major pathologies including mental retardation, chromosome instability syndromes, and various types of cancers. Owing to its critical influence, great potential lies in developing epigenetic therapies. In this regard, this review has highlighted mechanistic and structural interactions of the main epigenetic families with their targets, which will help to identify more efficient and safe drugs against several diseases. Full article
(This article belongs to the Special Issue Protein-DNA Interactions)
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Open AccessReview c-di-AMP: An Essential Molecule in the Signaling Pathways that Regulate the Viability and Virulence of Gram-Positive Bacteria
Genes 2017, 8(8), 197; doi:10.3390/genes8080197
Received: 26 June 2017 / Revised: 29 July 2017 / Accepted: 31 July 2017 / Published: 7 August 2017
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Abstract
Signal transduction pathways enable organisms to monitor their external environment and adjust gene regulation to appropriately modify their cellular processes. Second messenger nucleotides including cyclic adenosine monophosphate (c-AMP), cyclic guanosine monophosphate (c-GMP), cyclic di-guanosine monophosphate (c-di-GMP), and cyclic di-adenosine monophosphate (c-di-AMP) play key
[...] Read more.
Signal transduction pathways enable organisms to monitor their external environment and adjust gene regulation to appropriately modify their cellular processes. Second messenger nucleotides including cyclic adenosine monophosphate (c-AMP), cyclic guanosine monophosphate (c-GMP), cyclic di-guanosine monophosphate (c-di-GMP), and cyclic di-adenosine monophosphate (c-di-AMP) play key roles in many signal transduction pathways used by prokaryotes and/or eukaryotes. Among the various second messenger nucleotides molecules, c-di-AMP was discovered recently and has since been shown to be involved in cell growth, survival, and regulation of virulence, primarily within Gram-positive bacteria. The cellular level of c-di-AMP is maintained by a family of c-di-AMP synthesizing enzymes, diadenylate cyclases (DACs), and degradation enzymes, phosphodiesterases (PDEs). Genetic manipulation of DACs and PDEs have demonstrated that alteration of c-di-AMP levels impacts both growth and virulence of microorganisms. Unlike other second messenger molecules, c-di-AMP is essential for growth in several bacterial species as many basic cellular functions are regulated by c-di-AMP including cell wall maintenance, potassium ion homeostasis, DNA damage repair, etc. c-di-AMP follows a typical second messenger signaling pathway, beginning with binding to receptor molecules to subsequent regulation of downstream cellular processes. While c-di-AMP binds to specific proteins that regulate pathways in bacterial cells, c-di-AMP also binds to regulatory RNA molecules that control potassium ion channel expression in Bacillus subtilis. c-di-AMP signaling also occurs in eukaryotes, as bacterially produced c-di-AMP stimulates host immune responses during infection through binding of innate immune surveillance proteins. Due to its existence in diverse microorganisms, its involvement in crucial cellular activities, and its stimulating activity in host immune responses, c-di-AMP signaling pathway has become an attractive antimicrobial drug target and therefore has been the focus of intensive study in several important pathogens. Full article
(This article belongs to the Section Microbial Genetics and Genomics)
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