Arbitrariness in the genetic code is one of the main reasons for a linguistic approach to molecular biology: the genetic code is usually understood as an arbitrary relation between amino acids and nucleobases. However, from a semiotic point of view, arbitrariness should not be the only condition for definition of a code, consequently it is not completely correct to talk about "code" in this case. Yet we suppose that there exist a code in the process of protein synthesis, but on a higher level than the nucleic bases chains. Semiotically, a code should be always associated with a function and we propose to define the genetic code not only relationally (in basis of relation between nucleobases and amino acids) but also in terms of function (function of a protein as meaning of the code). Even if the functional definition of meaning in the genetic code has been discussed in the field of biosemiotics, its further implications have not been considered. In fact, if the function of a protein represents the meaning of the genetic code (the sign's object), then it is crucial to reconsider the notion of its expression (the sign) as well. In our contribution, we will show that the actual model of the genetic code is not the only possible and we will propose a more appropriate model from a semiotic point of view.

• Keywords
• Arbitrariness, Biosemiotics, Genetic code, Protein function, Semiotics,
• MeSH
• Amino Acids chemistry   MeSH
• Point Mutation MeSH
• DNA chemistry   MeSH
• Genetic Code * MeSH
• Histones chemistry   MeSH
• Models, Genetic MeSH
• Nucleotides genetics   MeSH
• RNA chemistry   MeSH
• Protein Folding MeSH
• Models, Theoretical MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Amino Acids MeSH
• DNA MeSH
• Histones MeSH
• Nucleotides MeSH
• RNA MeSH

A high degree of developmental plasticity enables plants to adapt to continuous, often unfavorable and unpredictable changes in their environment. At the molecular level, adaptive advantages for plants are primarily provided by epigenetic machinery including DNA methylation, histone modifications, and the activity of noncoding RNA molecules. Using a mass spectrometry-based proteomic approach, we examined the levels of acetylated histone peptide forms in Arabidopsis plants with a loss of function of histone deacetylase 6 (HDA6), and in plants germinated in the presence of HDA inhibitors trichostatin A (TSA) and sodium butyrate (NaB). Our analyses revealed particular lysine sites at histone sequences targeted by the HDA6 enzyme, and by TSA- and NaB-sensitive HDAs. Compared with plants exposed to drugs, more dramatic changes in the overall profiles of histone post-translational modifications were identified in hda6 mutants. However, loss of HDA6 was not sufficient by itself to induce hyperacetylation to the maximum degree, implying complementary activities of other HDAs. In contrast to hda6 mutants that did not exhibit any obvious phenotypic defects, the phenotypes of seedlings exposed to HDA inhibitors were markedly affected, showing that the effect of these drugs on early plant development is not limited to the modulation of histone acetylation levels.

• Keywords
• Arabidopsis thaliana, epigenetics, histone, mass spectrometry, post-translational modifications, sodium butyrate, trichostatin A,
• MeSH
• Arabidopsis genetics   growth & development   MeSH
• Histone Deacetylases genetics   MeSH
• Histone Code drug effects   genetics   MeSH
• Histone Deacetylase Inhibitors pharmacology   MeSH
• Germination genetics   MeSH
• Butyric Acid pharmacology   MeSH
• Hydroxamic Acids pharmacology   MeSH
• DNA Methylation drug effects   MeSH
• Arabidopsis Proteins antagonists & inhibitors   genetics   MeSH
• Proteomics * MeSH
• Gene Expression Regulation, Plant MeSH
• Seedlings drug effects   genetics   MeSH
• Gene Silencing MeSH
• Plant Development drug effects   genetics   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• AT5G63110 protein, Arabidopsis MeSH Browser
• Histone Deacetylases MeSH
• Histone Deacetylase Inhibitors MeSH
• Butyric Acid MeSH
• Hydroxamic Acids MeSH
• Arabidopsis Proteins MeSH
• trichostatin A MeSH Browser

Contrasting patterns of histone modifications between the X and Y chromosome in Silene latifolia show euchromatic histone mark depletion on the Y chromosome and indicate hyperactivation of one X chromosome in females. Silene latifolia (white campion) is a dioecious plant with heteromorphic sex chromosomes (24, XX in females and 24, XY in males), and a genetically degenerated Y chromosome that is 1.4 times larger than the X chromosome. Although the two sex chromosomes differ in their DNA content, information about epigenetic histone marks and evidence of their function are scarce. We performed immunolabeling experiments using antibodies specific for active and suppressive histone modifications as well as pericentromere-specific histone modifications. We show that the Y chromosome is partially depleted of histone modifications important for transcriptionally active chromatin, and carries these marks only in the pseudo-autosomal region, but that it is not enriched for suppressive and pericentromere histone marks. We also show that two of the active marks are specifically enriched in one of the X chromosomes in females and in the X chromosome in males. Our data support recent findings that genetic imprinting mediates dosage compensation of sex chromosomes in S. latifolia.

• Keywords
• Posttranslational histone modifications, Pseudo-autosomal region, Sex chromosomes,
• MeSH
• Chromosomes, Plant genetics   MeSH
• Epigenesis, Genetic * MeSH
• Histone Code genetics   MeSH
• Silene genetics   MeSH
• Publication type
• Journal Article MeSH

Telomeres, nucleoprotein structures at the ends of linear eukaryotic chromosomes, are crucial for the maintenance of genome integrity. In most plants, telomeres consist of conserved tandem repeat units comprising the TTTAGGG motif. Recently, non-canonical telomeres were described in several plants and plant taxons, including the carnivorous plant Genlisea hispidula (TTCAGG/TTTCAGG), the genus Cestrum (Solanaceae; TTTTTTAGGG), and plants from the Asparagales order with either a vertebrate-type telomere repeat TTAGGG or Allium genus-specific CTCGGTTATGGG repeat. We analyzed epigenetic modifications of telomeric histones in plants with canonical and non-canonical telomeres, and further in telomeric chromatin captured from leaves of Nicotiana benthamiana transiently transformed by telomere CRISPR-dCas9-eGFP, and of Arabidopsis thaliana stably transformed with TALE_telo C-3×GFP. Two combinatorial patterns of telomeric histone modifications were identified: (i) an Arabidopsis-like pattern (A. thaliana, G. hispidula, Genlisea nigrocaulis, Allium cepa, Narcissus pseudonarcissus, Petunia hybrida, Solanum tuberosum, Solanum lycopersicum) with telomeric histones decorated predominantly by H3K9me2; (ii) a tobacco-like pattern (Nicotiana tabacum, N. benthamiana, C. elegans) with a strong H3K27me3 signal. Our data suggest that epigenetic modifications of plant telomere-associated histones are related neither to the sequence of the telomere motif nor to the lengths of the telomeres. Nor the phylogenetic position of the species plays the role; representatives of the Solanaceae family are included in both groups. As both patterns of histone marks are compatible with fully functional telomeres in respective plants, we conclude that the described specific differences in histone marks are not critical for telomere functions.

• Keywords
• Arabidopsis thaliana, Nicotiana, chromatin, epigenetics, histone modification, telomeres,
• MeSH
• Arabidopsis genetics   MeSH
• Chromatin genetics   MeSH
• Epigenomics * MeSH
• Phylogeny MeSH
• Histone Code genetics   MeSH
• Plants genetics   MeSH
• Nicotiana genetics   MeSH
• Telomere genetics   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Chromatin MeSH

Epigenetic mechanisms have not been characterized in ticks despite their importance as vectors of human and animal diseases worldwide. The objective of this study was to characterize the histones and histone modifying enzymes (HMEs) of the tick vector Ixodes scapularis and their role during Anaplasma phagocytophilum infection. We first identified 5 histones and 34 HMEs in I. scapularis in comparison with similar proteins in model organisms. Then, we used transcriptomic and proteomic data to analyze the mRNA and protein levels of I. scapularis histones and HMEs in response to A. phagocytophilum infection of tick tissues and cultured cells. Finally, selected HMEs were functionally characterized by pharmacological studies in cultured tick cells. The results suggest that A. phagocytophilum manipulates tick cell epigenetics to increase I. scapularis p300/CBP, histone deacetylase, and Sirtuin levels, resulting in an inhibition of cell apoptosis that in turn facilitates pathogen infection and multiplication. These results also suggest that a compensatory mechanism might exist by which A. phagocytophilum manipulates tick HMEs to regulate transcription and apoptosis in a tissue-specific manner to facilitate infection, but preserving tick fitness to guarantee survival of both pathogens and ticks. Our study also indicates that the pathogen manipulates arthropod and vertebrate cell epigenetics in similar ways to inhibit the host response to infection. Epigenetic regulation of tick biological processes is an essential element of the infection by A. phagocytophilum and the study of the mechanisms and principal actors involved is likely to provide clues for the development of anti-tick drugs and vaccines.

• Keywords
• Anaplasma, epigenetics, histone, histone modifying enzyme, pathogen, tick,
• MeSH
• Anaplasma phagocytophilum genetics   MeSH
• Apoptosis genetics   MeSH
• Cell Line MeSH
• Epigenesis, Genetic * MeSH
• Histone Code genetics   MeSH
• Histones genetics   metabolism   MeSH
• Insect Vectors genetics   MeSH
• Host-Pathogen Interactions genetics   MeSH
• Ixodes genetics   MeSH
• Humans MeSH
• RNA, Messenger biosynthesis   genetics   MeSH
• p300-CBP Transcription Factors biosynthesis   genetics   MeSH
• Transcriptome genetics   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Histones MeSH
• RNA, Messenger MeSH
• p300-CBP Transcription Factors MeSH

• MeSH
• DNA metabolism   MeSH
• Genetic Code * MeSH
• Histones metabolism   MeSH
• Humans MeSH
• Protein Biosynthesis MeSH
• Antibody Formation MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• DNA MeSH
• Histones MeSH

• MeSH
• Arginine analysis   MeSH
• Bacterial Proteins biosynthesis   MeSH
• RNA, Bacterial biosynthesis   MeSH
• Time Factors MeSH
• Enzyme Induction MeSH
• Escherichia coli drug effects   enzymology   growth & development   metabolism   MeSH
• Galactosidases biosynthesis   MeSH
• Genetic Code MeSH
• Histones analysis   pharmacology   MeSH
• Carbon Isotopes MeSH
• Culture Media MeSH
• Leucine metabolism   MeSH
• Lysine analysis   MeSH
• RNA, Messenger biosynthesis   MeSH
• Genetics, Microbial MeSH
• Cattle MeSH
• Thymine metabolism   MeSH
• Thymus Gland MeSH
• Uracil metabolism   MeSH
• Animals MeSH
• Check Tag
• Cattle MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Arginine MeSH
• Bacterial Proteins MeSH
• RNA, Bacterial MeSH
• Galactosidases MeSH
• Histones MeSH
• Carbon Isotopes MeSH
• Culture Media MeSH
• Leucine MeSH
• Lysine MeSH
• RNA, Messenger MeSH
• Thymine MeSH
• Uracil MeSH

Reshaping of the chromatin landscape under oxidative stress is of paramount importance for mounting an effective stress response. Unbiased systemic identification and quantification of histone marks is crucial for understanding the epigenetic component of plant responses to adverse environmental conditions. We describe a detailed method for isolation of plant histones and subsequent bottom-up proteomics approach for characterization of acetylation and methylation status. By performing label-free quantitative mass spectrometry analysis, relative abundances of histone marks can be statistically compared between experimental conditions.

• Keywords
• Acetylation, Arabidopsis, Epigenetics, Histone posttranslational modifications, Histone propionylation, Mass spectrometry, Methylation, Nicotiana, Solanum,
• MeSH
• Acetylation MeSH
• Histone Code MeSH
• Histones * metabolism   MeSH
• Methylation MeSH
• Protein Processing, Post-Translational * MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Histones * MeSH

Hepatocellular carcinomas (HCCs) contain a sub-population of cancer stem cells (CSCs) that are responsible for tumor relapse, metastasis, and chemoresistance. We recently showed that loss of macroH2A1, a variant of the histone H2A and an epigenetic regulator of stem-cell function, in HCC leads to CSC-like features such as resistance to chemotherapeutic agents and growth of large and relatively undifferentiated tumors in xenograft models. These HCC cells silenced for macroH2A1 also exhibited stem-like metabolic changes consistent with enhanced glycolysis. However, there is no consensus as to the metabolic characteristics of CSCs that render them adaptable to microenvironmental changes by conveniently shifting energy production source or by acquiring intermediate metabolic phenotypes. Here, we assessed long-term proliferation, energy metabolism, and central carbon metabolism in human hepatoma HepG2 cells depleted in macroH2A1. MacroH2A1-depleted HepG2 cells were insensitive to serum exhaustion and showed two distinct, but interdependent changes in glucose and lipid metabolism in CSCs: (1) massive upregulation of acetyl-coA that is transformed into enhanced lipid content and (2) increased activation of the pentose phosphate pathway, diverting glycolytic intermediates to provide precursors for nucleotide synthesis. Integration of metabolomic analyses with RNA-Seq data revealed a critical role for the Liver X Receptor pathway, whose inhibition resulted in attenuated CSCs-like features. These findings shed light on the metabolic phenotype of epigenetically modified CSC-like hepatic cells, and highlight a potential approach for selective therapeutic targeting.

• Keywords
• Histone variants, cancer stem cells, hepatocellular carcinoma,
• MeSH
• Hep G2 Cells MeSH
• Epigenesis, Genetic * MeSH
• HEK293 Cells MeSH
• Carcinoma, Hepatocellular genetics   metabolism   MeSH
• Histone Code * MeSH
• Humans MeSH
• Lipid Metabolism * MeSH
• Carbohydrate Metabolism * MeSH
• Neoplastic Stem Cells metabolism   MeSH
• Liver Neoplasms metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Understanding the epigenetics of tumor cells is of clinical significance for the treatment of cancer, and thus, chemists have focused their efforts on the synthesis of new generation of inhibitors of histone deacetylases (HDACs) or methylation-specific enzymes as novel important anti-cancer drugs. Here, we tested whether the histone signature and DNA methylation in multiple myeloma (MM) and leukemia cells is tumor-specific as compared with that in non-malignant lymphoblastoid cells. We observed a distinct histone signature in c-myc, Mcl-1, and ribosomal gene loci in MOLP8 MM and K562 leukemia cells, when compared with lymphoblastoid cells. Histone and DNA methylation patterns in MOLP8 cells were partially modified by the clinically promising HDAC inhibitor, vorinostat. In comparison with lymphoblastoid WIL2NS cells, MOLP8 cells and K562 cells were characterized by an absence of the gene silencing marker H3K9me2 in the c-myc and ribosomal genes. However, high levels of H3K27me3 were detected in the promoters and coding regions of selected genomic regions in these cells. Treatment by vorinostat increased the level of DNA methylation at the c-myc promoter, and this alteration was accompanied by a decrease in c-MYC protein. In MOLP8 cells, vorinostat significantly increased the H3K9 acetylation in the Mcl-1 coding regions and promoter. Both MOLP8 and K562 leukemia cells were characterized by decreased levels of H3K9me2 in the Mcl-1 gene as compared with lymphoblastoid WIL2NS cells. Lower levels of H3K9me1 in the Mcl-1 promoter, however, were specific for MM cells as compared with the other cell types studied. In other MM and leukemia cell lines, COLO677, OPM2, and U937, the ribosomal genes were less prone to epigenetic heterogeneity as compared to the c-myc and Mcl-1 proto-oncogenes. Taken together, these data describe both tumor-specific and loci-specific histone signature and DNA methylation profiles.

• MeSH
• Chromatin Immunoprecipitation MeSH
• Epigenesis, Genetic genetics   MeSH
• Fluorescent Antibody Technique MeSH
• Histones genetics   MeSH
• Leukemia genetics   MeSH
• Humans MeSH
• DNA Methylation * MeSH
• Multiple Myeloma genetics   MeSH
• Cell Line, Tumor MeSH
• Promoter Regions, Genetic genetics   MeSH
• Gene Expression Profiling * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Histones MeSH