Sepsis is a life-threatening organ dysfunction caused by dysregulated body response to infection. It is also one of the major causes of death in critically ill patients. Over the past few years, despite the continuous improvement in the treatment of sepsis, there is no specific treatment, clinical morbidity and mortality are still rising. Therefore, finding effective methods to treat sepsis and reduce mortality is an urgent clinical problem. Histone modification is an epigenetic modification that produces heritable phenotypic changes without altering the DNA sequence. In recent years, many studies have shown that histone modification is closely related to sepsis. This review discusses the mechanism of histone modification in the pathogenesis of sepsis from the aspects of inflammatory factors, signaling pathways, and macrophage polarization, in aimed to provide reference for the clinical treatment of sepsis.
Humans ; Histone Code ; Sepsis/metabolism* ; Critical Illness ; Macrophage Activation

It is well established that there is a heritable element of susceptibility to chronic human ailments, yet there is compelling evidence that some components of such heritability are transmitted through non-genetic factors. Due to the complexity of reproductive processes, identifying the inheritance patterns of these factors is not easy. But little doubt exists that besides the genomic backbone, a range of epigenetic cues affect our genetic programme. The inter-generational transmission of epigenetic marks is believed to operate via four principal means that dramatically differ in their information content: DNA methylation, histone modifications, microRNAs and nucleosome positioning. These epigenetic signatures influence the cellular machinery through positive and negative feedback mechanisms either alone or interactively. Understanding how these mechanisms work to activate or deactivate parts of our genetic programme not only on a day-to-day basis but also over generations is an important area of reproductive health research.
Cues ; DNA Methylation ; Epigenomics* ; Family Characteristics ; Histone Code ; Humans ; Inheritance Patterns ; MicroRNAs ; Nucleosomes ; Reproductive Health*

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

Histone modifications are key epigenetic regulatory features that have important roles in many cellular events. Lysine methylations mark various sites on the tail and globular domains of histones and their levels are precisely balanced by the action of methyltransferases (‘writers’) and demethylases (‘erasers’). In addition, distinct effector proteins (‘readers’) recognize specific methyl-lysines in a manner that depends on the neighboring amino-acid sequence and methylation state. Misregulation of histone lysine methylation has been implicated in several cancers and developmental defects. Therefore, histone lysine methylation has been considered a potential therapeutic target, and clinical trials of several inhibitors of this process have shown promising results. A more detailed understanding of histone lysine methylation is necessary for elucidating complex biological processes and, ultimately, for developing and improving disease treatments. This review summarizes enzymes responsible for histone lysine methylation and demethylation and how histone lysine methylation contributes to various biological processes.
Biological Processes ; Epigenomics ; Histone Code ; Histones* ; Lysine* ; Methylation* ; Methyltransferases ; Tail ; Writing*

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

The ovary is the reproductive organ of female mammals, which is responsible for producing mature eggs and secreting sex hormones. The regulation of ovarian function involves the ordered activation and repression of genes related to cell growth and differentiation. In recent years, it has been found that histone posttranslational modification can affect DNA replication, damage repair and gene transcriptional activity. Some regulatory enzymes mediating histone modification are co-activators or co-inhibitors associated with transcription factors, which play important roles in the regulation of ovarian function and the development of ovary-related diseases. Therefore, this review outlines the dynamic patterns of common histone modifications (mainly acetylation and methylation) during the reproductive cycle and their regulation of gene expression for important molecular events, focusing on the mechanisms of follicle development and sex hormone secretion and function. For example, the specific dynamics of histone acetylation are important for the arrest and resumption of meiosis in oocytes, while histone (especially H3K4) methylation affects the maturation of oocytes by regulating their chromatin transcriptional activity and meiotic progression. Besides, histone acetylation or methylation can also promote the synthesis and secretion of steroid hormones before ovulation. Finally, the abnormal histone posttranslational modifications in the development of two common ovarian diseases (premature ovarian insufficiency and polycystic ovary syndrome) are briefly described. It will provide a reference basis for understanding the complex regulation mechanism of ovarian function and further exploring the potential therapeutic targets of related diseases.
Female ; Animals ; Histone Code ; Histones ; Protein Processing, Post-Translational ; Ovary ; Oocytes ; Mammals

Transcriptional regulation of a gene is not always correlated with genetic information inherited from parents because the transcription of specific genes is often governed by the modification of chromatin structure. The study of transcriptional regulation by modifying chromatin structure is well-known as "epigenetics". Several methods involved in the modification of chromatin structure have been developed in the mammalian species during evolution. Among those methods, methylations of specific DNA region or histone are often used to control specific gene transcription. Therefore, understanding the activity of proteins involved in DNA or histone methylation is an initial step to control the transcriptional activity of a specific gene. Polycomb group (PcG) proteins were known to be repressors of transcription of a specific gene by creating and maintaining methylation or ubiquitination of the specific region of histone. Dependent on the target histone, the activity of PcG proteins effects on the development of specific lineage cells or the activity of specific cell types. In this review, the function, expression and activity of PcG proteins related with the development or activation of T cells are discussed.
Chromatin ; DNA ; Epigenomics ; Genes, vif ; Histone Code ; Histones ; Humans ; Methylation ; Parents ; Polycomb-Group Proteins ; Proteins ; T-Lymphocytes ; Ubiquitin ; Ubiquitination

Breast cancer has the highest incidence among all malignancies diagnosed in women. Therapies have significantly improved over the years due to extensive molecular and clinical research; in a large number of cases, targeted therapies have provided better prognosis. However, one specific subtype remains elusive to targeted therapies–the triple-negative breast cancer. This immunohistochemically defined subtype is resistant to both endocrine and targeted therapies, leading to its poor prognosis. A field that is of great promise in current cancer research is epigenetics. By studying the epigenetic mechanisms underlying tumorigenesis–DNA methylation, histone modifications, and noncoding RNAs–advances in cancer treatment, diagnosis, and prevention are possible. This review aims to synthesize the epigenetic discoveries that have been made related to the triple-negative breast cancer.
Breast Neoplasms* ; Breast* ; Diagnosis ; DNA Methylation ; Epigenomics* ; Female ; Histone Code ; Humans ; Incidence ; Methylation ; Prognosis ; RNA, Untranslated ; Triple Negative Breast Neoplasms

OBJECTIVE: Depression is associated with various environmental risk factors such as stress, childhood maltreatment experiences, and stressful life events. Current approaches to assess the pathophysiology of depression, such as epigenetics and gene-environment (GxE) interactions, have been widely leveraged to determine plausible markers, genes, and variants for the risk of developing depression. METHODS: We focus on the most recent developments for genomic research in epigenetics and GxE interactions. RESULTS: In this review, we first survey a variety of association studies regarding depression with consideration of GxE interactions. We then illustrate evidence of epigenetic mechanisms such as DNA methylation, microRNAs, and histone modifications to influence depression in terms of animal models and human studies. Finally, we highlight their limitations and future directions. CONCLUSION: In light of emerging technologies in artificial intelligence and machine learning, future research in epigenetics and GxE interactions promises to achieve novel innovations that may lead to disease prevention and future potential therapeutic treatments for depression.
Artificial Intelligence ; Biomarkers ; Depression ; DNA Methylation ; Epigenomics ; Gene-Environment Interaction ; Histone Code ; Humans ; Machine Learning ; MicroRNAs ; Models, Animal ; Risk Factors

In previous studies, we demonstrated that some sites in the first intron likely regulate gene expression. In the present work, we sought to further confirm the functional relevance of first intron sites by estimating the quantity of rare alleles in the first intron. A basic hypothesis posited herein is that genomic regions carrying more functionally important sites will have a higher proportion of rare alleles. We estimated the proportions of rare single nucleotide polymorphisms with a minor allele frequency < 0.01 located in several histone marks in the first introns of various genes, and compared them with those in other introns and those in 2-kb upstream regions. As expected, rare alleles were found to be significantly enriched in most of the regulatory sites located in the first introns. Meanwhile, transcription factor binding sites were significantly more enriched in the 2-kb upstream regions (i.e., the regions of putative promoters of genes) than in the first introns. These results strongly support our proposal that the first intron sites of genes may have important regulatory functions in gene expression independent of promoters.
Alleles ; Binding Sites ; Chromatin ; Epigenomics ; Gene Expression ; Gene Frequency ; Histone Code ; Introns ; Polymorphism, Single Nucleotide ; Transcription Factors