Genetic code expansion (GCE) allows the incorporation of unnatural amino acids into proteins via using stop codons. GCE may achieve site-specific labeling of proteins in combination with the click reaction. Compared with other labeling tools such as fluorescent proteins and tagged antibodies, the compound molecules used in protein labeling by GCE technology are smaller, and therefore, may less interfere the conformational structure of proteins. In addition, through click reaction, GCE allows a 1:1 stoichiometric ratio of the target protein molecule and the fluorescent dye, and the protein can be quantified based on the fluorescence intensity. Thus, GCE technology has great advantages in the researches that require the exposition of living cells under high laser power for longer time, for example, in the context of single molecule tracing and super-resolution microscopic imaging. Meanwhile, this technology lays the foundation for improving the accuracy of positioning and molecule counting in the imaging process of living cells. This review summarized the GCE technology and its recent applications in functionally characterizing, labeling and imaging of proteins.
Amino Acids/chemistry* ; Fluorescent Dyes/chemistry* ; Genetic Code ; Proteins/chemistry*

Mammalian fertilization begins with the fusion of two specialized gametes, followed by major epigenetic remodeling leading to the formation of a totipotent embryo. During the development of the pre-implantation embryo, precise reprogramming progress is a prerequisite for avoiding developmental defects or embryonic lethality, but the underlying molecular mechanisms remain elusive. For the past few years, unprecedented breakthroughs have been made in mapping the regulatory network of dynamic epigenomes during mammalian early embryo development, taking advantage of multiple advances and innovations in low-input genome-wide chromatin analysis technologies. The aim of this review is to highlight the most recent progress in understanding the mechanisms of epigenetic remodeling during early embryogenesis in mammals, including DNA methylation, histone modifications, chromatin accessibility and 3D chromatin organization.
Animals ; Chromatin Assembly and Disassembly ; DNA Methylation ; DNA Transposable Elements ; Embryo, Mammalian ; Embryonic Development/genetics* ; Epigenesis, Genetic ; Epigenome ; Female ; Fertilization/physiology* ; Gene Expression Regulation, Developmental ; Histone Code ; Histones/metabolism* ; Male ; Mice ; Oocytes/metabolism* ; Spermatozoa/metabolism*

Enhancers activate transcription in a distance-, orientation-, and position-independent manner, which makes them difficult to be identified. Self-transcribing active regulatory region sequencing (STARR-seq) measures the enhancer activity of millions of DNA fragments in parallel. Here we used STARR-seq to generate a quantitative global map of rice enhancers. Most enhancers were mapped within genes, especially at the 5' untranslated regions (5'UTR) and in coding sequences. Enhancers were also frequently mapped proximal to silent and lowly-expressed genes in transposable element (TE)-rich regions. Analysis of the epigenetic features of enhancers at their endogenous loci revealed that most enhancers do not co-localize with DNase I hypersensitive sites (DHSs) and lack the enhancer mark of histone modification H3K4me1. Clustering analysis of enhancers according to their epigenetic marks revealed that about 40% of identified enhancers carried one or more epigenetic marks. Repressive H3K27me3 was frequently enriched with positive marks, H3K4me3 and/or H3K27ac, which together label enhancers. Intergenic enhancers were also predicted based on the location of DHS regions relative to genes, which overlap poorly with STARR-seq enhancers. In summary, we quantitatively identified enhancers by functional analysis in the genome of rice, an important model plant. This work provides a valuable resource for further mechanistic studies in different biological contexts.
Acetylation ; Base Sequence ; Deoxyribonuclease I ; metabolism ; Enhancer Elements, Genetic ; Epigenesis, Genetic ; Genes, Plant ; Genomics ; methods ; Histone Code ; genetics ; Histones ; metabolism ; Models, Genetic ; Oryza ; genetics ; Promoter Regions, Genetic ; genetics ; Repetitive Sequences, Nucleic Acid ; genetics ; Sequence Analysis, DNA ; Transcription, Genetic

It has been increasingly recognized that the pathogenesis of B-cell lymphoma closely relates to the epigenetic disregulations. Epigenetics is a subdiscipline, which means heritable changes in gene expressions without alterations in the DNA sequence, and the DNA methylation, histone modification and miRNA maily were involved. Histone modification is the most important epigenetic modification, the researches showed that the aberrant histone modification is the important pathogenesis in B-cell lymphoma, especially the aberrant histone methylation and acetylation. In the meantime, the tumor can be treated by changing the epigenetic modification, which become a research hotpoint. This review summarizes the pathogenesis of B cell lymphoma and discusses the epigenetic treatment of B cell lymphoma mainly in terms of histone modification regulation for B cell development in the germinal center and mutation of histone madification enzymes.
DNA Methylation ; Epigenesis, Genetic ; Histone Code ; Histones ; Humans ; Lymphoma, B-Cell

Epigenetic modification, especially histone modification, plays an important role in maintaining plant genome stability, regulating gene expression and promoting regeneration in vitro. MtSERK1 is an important marker gene involved in establishing of embryogenic callus during in vitro regeneration of Medicago truncatula. In order to understand the regulation Epigenetic modification, especially histone modification, plays an important role in maintaining plant genome stability, regulating gene expression and promoting regeneration in vitro. MtSERK1 is an important marker gene involved in establishing of embryogenic callus during in vitro regeneration of Medicago truncatula. In order to understand the regulation relationship between dynamic histone modification and MtSERK1s expression during the processes of in vitro organogenesis, the expression of MtSERK1 was analyzed by qRT-PCR, and the modification status of H3K9me2, H3K4me3 and H3K9ac in the promoter region and different regions included in the gene body was analyzed by chromatin immunoprecipitation (ChIP). We found expression activation of MtSERK1 was related to the dynamic changes of histone H3K4me3 and H3K9ac in the 5' and 3' regions. This study will provide important theoretical guidance for understanding of the regulatory mechanism of MtSERK1 and also for establishing efficient genetic transformation system of Medicago truncatula.
Epigenesis, Genetic ; Gene Expression Regulation, Plant ; Genome, Plant ; Histone Code ; Medicago truncatula ; genetics ; growth & development ; Protein Kinases ; genetics ; Regeneration

Alteration of apoptosis is related with progression and recurrence of atypical meningiomas (AMs). However, no comprehensive study has been conducted regarding histone modification regulating apoptosis in AMs. This study aimed to determine the prognostic values of certain apoptosis-associated factors, and examine the role of histone modification on apoptosis in AMs. The medical records of 67 patients with AMs, as diagnosed during recent 13 yr, were reviewed retrospectively. Immunohistochemical staining was performed on archived paraffin-embedded tissues for pro-apoptotic factors (CASP3, IGFBP, TRAIL-R1, BAX, and XAF1), anti-apoptotic factors (survivin, ERK, RAF1, MDM2, and BCL2), and the histone modifying enzymes (MLL2, RIZ, EZH1, NSD2, KDM5c, JMJD2a, UTX, and JMJD5). Twenty-six (38.8%) patients recurred during the follow-up period (mean duration 47.7 months). In terms of time-to-recurrence (TTR), overexpression of CASP3, TRAIL-R1, and BAX had a longer TTR than low expression, and overexpression of survivin, MDM2, and BCL2 had a shorter TTR than low expression (P<0.05). Additionally, overexpression of MLL2, UTX, and JMJ5 had shorter TTRs than low expression, and overexpression of KDM5c had a longer TTR than low expression. However, in the multi-variate analysis of predicting factors for recurrence, low expression of CASP3 (P<0.001), and BAX (P<0.001), and overexpression of survivin (P=0.007), and MDM2 (P=0.037) were associated with recurrence independently, but any enzymes modifying histone were not associated with recurrence. Conclusively, this study suggests certain apoptosis-associated factors should be associated with recurrence of AMs, which may be regulated epigenetically by histone modifying enzymes.
Adult ; Aged ; Aged, 80 and over ; Apoptosis/*genetics ; Apoptosis Regulatory Proteins/genetics ; Epigenesis, Genetic/genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Histone Code/genetics ; Histone Demethylases/*genetics ; Histone-Lysine N-Methyltransferase/*genetics ; Humans ; Longitudinal Studies ; Male ; Meningeal Neoplasms/*genetics/pathology ; Meningioma/*genetics/pathology ; Middle Aged ; Neoplasm Recurrence, Local/*genetics

Watson and Crick published a paper on the double helical structure of DNA in Nature in April 25, 1953. The human genome is contained in the 23 pairs of chromosomes and in the mitochondrial DNA of each cell. The Human Genome Project was launched in 1990 under the direction of Watson and concluded in 2003, on the 50th anniversary of Watson and Crick paper. Over 6 billion of nucleotides of genetic codes are in single cells. There are 23,000 protein coding genes and the remainder are non-coding DNA, regulatory DNA. Since the completion of Human Genome Project, these huge genomic information has been translated into clinically usable medical information. With the advent of massively parallel DNA sequencing, known as next generation DNA sequencing, the cost and turn-around time were significantly reduced so that the era of Whole Genome Sequencing entered into hospitals and medical clinics. On June 16, 2014 American Society of Human Genetics revised its mission statement as follows. "Our mission is to advance human genetics in science, health and society through research, education and advocacy". Finally medical genetics nestled its roots in the midst of genetics and genomics.
Anniversaries and Special Events ; Clinical Coding ; Clinical Medicine* ; DNA ; DNA, Mitochondrial ; Education ; Genetic Code ; Genetics ; Genetics, Medical ; Genome ; Genome, Human ; Genomics ; Human Genome Project ; Humans ; Missions and Missionaries ; Nucleotides ; Sequence Analysis, DNA*

Periodontitis is a common oral disease that is characterized by infection and inflammation of the tooth supporting tissues. While its incidence is highly associated with outgrowth of the pathogenic microbiome, some patients show signs of predisposition and quickly fall into recurrence after treatment. Recent research using genetic associations of candidates as well as genome-wide analysis highlights that variations in genes related to the inflammatory response are associated with an increased risk of periodontitis. Intriguingly, some of the genes are regulated by epigenetic modifications, supposedly established and reprogrammed in response to environmental stimuli. In addition, the treatment with epigenetic drugs improves treatment of periodontitis in a mouse model. In this review, we highlight some of the recent progress identifying genetic factors associated with periodontitis and point to promising approaches in epigenetic research that may contribute to the understanding of molecular mechanisms involving different responses in individuals and the early detection of predispositions that may guide in future oral treatment and disease prevention.
Animals ; DNA Methylation ; Epigenomics ; Genetic Variation ; Histone Code ; Humans ; Inflammation ; Metagenome ; Mice ; Periodontitis ; Recurrence ; Tooth

Catalytic Domain ; genetics ; Dual Specificity Phosphatase 3 ; chemistry ; genetics ; metabolism ; Genetic Code ; Humans ; Mutation ; Phosphorylation ; Protein Conformation ; Signal Transduction ; genetics ; Structure-Activity Relationship ; Tyrosine ; analogs & derivatives ; chemistry ; genetics

As the pathogenic bacterial virulence and avirulence factors, transcription activator like (TAL) effectors of Xanthomonas can resulted in the host diseases or resistance responses. TAL effectors can specifically bind the target DNA of host plant with a novel protein-DNA binding pattern in which two amino acids recognize one nucleotide. The complexities of TAL-DNA binding have the feasibility in use of gene therapy through homologous recombination and site-specific mutation. By using the molecular recognition code between TAL-effectors and host target genes, we can exploit both the susceptible and resistance genes; broad spectrum resistance induced by multiple TAL effectors could also be manipulated. Deeper insight in the area of protein-DNA binding mechanism will benefit the application in the biomedical engineering and agricultural engineering. This article reviews the findings and functions of TAL effectors, the binding specificity and recognition code between TAL-effectors and host target genes. The possible applications and future prospects of the molecular recognition code have been discussed.
Base Sequence ; DNA, Plant ; metabolism ; Genes, Plant ; Genetic Code ; genetics ; Host-Pathogen Interactions ; Molecular Sequence Data ; Plant Diseases ; genetics ; prevention & control ; Transcriptional Activation ; Virulence Factors ; genetics ; metabolism ; Xanthomonas ; genetics ; pathogenicity