A review of epigenetic changes in asthma: methylation and acetylation

Several studies show that childhood and adulthood asthma and its symptoms can be modulated through epigenetic modifications. Epigenetic changes are inheritable modifications that can modify the gene expression without changing the DNA sequence. The most common epigenetic alternations consist of DNA methylation and histone modifications. How these changes lead to asthmatic phenotype or promote the asthma features, in particular by immune pathways regulation, is an understudied topic. Since external effects, like exposure to tobacco smoke, air pollution, and drugs, influence both asthma development and the epigenome, elucidating the role of epigenetic changes in asthma is of great importance. This review presents available evidence on the epigenetic process that drives asthma genes and pathways, with a particular focus on DNA methylation, histone methylation, and acetylation. We gathered and assessed studies conducted in this field over the past two decades. Our study examined asthma in different aspects and also shed light on the limitations and the important factors involved in the outcomes of the studies. To date, most of the studies in this area have been carried out on DNA methylation. Therefore, the need for diagnostic and therapeutic applications through this molecular process calls for more research on the histone modifications in this disease.

Impaired Regulation of Histone Methylation and Acetylation Underlies Specific Neurodevelopmental Disorders

Epigenetic processes are critical for governing the complex spatiotemporal patterns of gene expression in neurodevelopment. One such mechanism is the dynamic network of post-translational histone modifications that facilitate recruitment of transcription factors or even directly alter chromatin structure to modulate gene expression. This is a tightly regulated system, and mutations affecting the function of a single histone-modifying enzyme can shift the normal epigenetic balance and cause detrimental developmental consequences. In this review, we will examine select neurodevelopmental conditions that arise from mutations in genes encoding enzymes that regulate histone methylation and acetylation. The methylation-related conditions discussed include Wiedemann-Steiner, Kabuki, and Sotos syndromes, and the acetylation-related conditions include Rubinstein-Taybi, KAT6A, genitopatellar/Say-Barber-Biesecker-Young-Simpson, and brachydactyly mental retardation syndromes. In particular, we will discuss the clinical/phenotypic and genetic basis of these conditions and the model systems that have been developed to better elucidate cellular and systemic pathological mechanisms.

Role of the Epigenome in Heart Failure

Gene expression is needed for the maintenance of heart function under normal conditions and in response to stress. Each cell type of the heart has a specific program controlling transcription. Different types of stress induce modifications of these programs and, if prolonged, can lead to altered cardiac phenotype and, eventually, to heart failure. The transcriptional status of a gene is regulated by the epigenome, a complex network of DNA and histone modifications. Until a few years ago, our understanding of the role of the epigenome in heart disease was limited to that played by histone deacetylation. But over the last decade, the consequences for the maintenance of homeostasis in the heart and for the development of cardiac hypertrophy of a number of other modifications, including DNA methylation and hydroxymethylation, histone methylation and acetylation, and changes in chromatin architecture, have become better understood. Indeed, it is now clear that many levels of regulation contribute to defining the epigenetic landscape required for correct cardiomyocyte function, and that their perturbation is responsible for cardiac hypertrophy and fibrosis. Here, we review these aspects and draw a picture of what epigenetic modification may imply at the therapeutic level for heart failure.

Epigenetic Regulators of Mesenchymal Stem/Stromal Cell Lineage Determination

Purpose of Review Although many signalling pathways have been discovered to be essential in mesenchymal stem/stromal (MSC) differentiation, it has become increasingly clear in recent years that epigenetic regulation of gene transcription is a vital component of lineage determination, encompassing diet, lifestyle and parental influences on bone, fat and cartilage development. Recent Findings This review discusses how specific enzymes that modify histone methylation and acetylation or DNA methylation orchestrate the differentiation programs in lineage determination of MSC and the epigenetic changes that facilitate development of bone related diseases such as osteoporosis. The review also describes how environmental factors such as mechanical loading influence the epigenetic signatures of MSC, and how the use of chemical agents or small peptides can regulate epigenetic drift in MSC populations during ageing and disease. Summary Epigenetic regulation of MSC lineage commitment is controlled through changes in enzyme activity, which modifies DNA and histone residues leading to alterations in chromatin structure. The co-ordinated epigenetic regulation of transcriptional activation and repression act to mediate skeletal tissue homeostasis, where deregulation of this process can lead to bone loss during ageing or osteoporosis.

Redox Components: Key Regulators of Epigenetic Modifications in Plants

Epigenetic modifications including DNA methylation, histone modifications, and chromatin remodeling are crucial regulators of chromatin architecture and gene expression in plants. Their dynamics are significantly influenced by oxidants, such as reactive oxygen species (ROS) and nitric oxide (NO), and antioxidants, like pyridine nucleotides and glutathione in plants. These redox intermediates regulate the activities and expression of many enzymes involved in DNA methylation, histone methylation and acetylation, and chromatin remodeling, consequently controlling plant growth and development, and responses to diverse environmental stresses. In recent years, much progress has been made in understanding the functional mechanisms of epigenetic modifications and the roles of redox mediators in controlling gene expression in plants. However, the integrated view of the mechanisms for redox regulation of the epigenetic marks is limited. In this review, we summarize recent advances on the roles and mechanisms of redox components in regulating multiple epigenetic modifications, with a focus of the functions of ROS, NO, and multiple antioxidants in plants.

Epigenetic Modification in Macrophages: A Promising Target for Tumor and Inflammation-associated Disease Therapy

Macrophages are essential for supporting tissue homeostasis, regulating immune response, and promoting tumor progression. Due to its heterogeneity, macrophages have different phenotypes and functions in various tissues and diseases. It is becoming clear that epigenetic modification playing an essential role in determining the biological behavior of cells. In particular, changes of DNA methylation, histone methylation and acetylation regulated by the corresponding epigenetic enzymes, can directly control macrophages differentiation and change their functions under different conditions. In addition, epigenetic enzymes also have become anti-tumor targets, such as HDAC, LSD1, DNMT, and so on. In this review, we presented an overview of the latest progress in the study of macrophages phenotype and function regulated by epigenetic modifications, including DNA methylation and histone modifications, to better understand how epigenetic modification controls macrophages phenotype and function in inflammation-associated diseases, and the application prospect in anti-tumor.