Single-cell multi-omic detection of DNA methylation and histone modifications reconstructs the dynamics of epigenomic maintenance

Epigenetics in evolution and disease

Introduction: Epigenetics and neuropsychiatric diseases

In 2014, Facebook and Apple announced that they would pay for female employees to have their oocytes frozen to allow them to delay having children and instead focus on their careers. Whatever motivated the companies to make their offers, the fact that they did so highlights a prevalent problem faced by many young women: Their most fertile years are also a crucial period for building a career, when time off work may disadvantage them. > … cryopreservation is known to affect cell survival after thawing, which can have an impact on the subsequent clinical applications of frozen cells. To fulfill their offers, Facebook and Apple will need to offer their employees access to cryopreservation technologies that profoundly change the dynamics of family planning. Such technologies are not new, but work over the past decades has been aimed at increasing safety and efficacy and has reduced costs to the point that companies can now offer cryopreservation as a way to attract and retain female workers. Of course, the potential of cryopreservation goes far beyond freezing the eggs or sperm of ambitious young technology workers—it is a ubiquitous technology used in research and medicine for a wide variety of applications (Fig 1). For example, cryopreservation is used to store and transport biological material, including adult stem cells or stem cells from umbilical cord blood or bone marrow—both of which can later be used to treat disease or extend lifespan in the same patient—blood donations, especially of rare blood types, tissues, and organs. It is also offered as a crucial service for cancer patients to preserve their gametes before they undergo therapy that may render them infertile and, generally used in assisted reproduction to store oocytes, fertilized eggs, or embryos. Cryopreservation can contribute to environmental preservation efforts, where it is used to conserve the …

A review of research shows that methylation in plants is more complex and sophisticated than in microorganisms and animals. Overall, studies on the effects of abiotic stress on epigenetic modifications in plants are still scarce and limited to few species. Epigenetic regulation of plant responses to environmental stresses has not been elucidated. This study summarizes key effects of abiotic stressors on DNA methylation and histone modifications in plants. Plant DNA methylation and histone modifications in responses to abiotic stressors varied and depended on the type and level of stress, plant tissues, age, and species. A critical analysis of the literature available revealed that 44% of the epigenetic modifications induced by abiotic stressors in plants involved DNA hypomethylation, 40% DNA hypermethylation, and 16% histone modification. The epigenetic changes in plants might be underestimated since most authors used methods such as methylation-sensitive amplification polymorphism (MSAP), High performance liquid chromatography (HPLC), and immunolabeling that are less sensitive compared to bisulfite sequencing and single-base resolution methylome analyses. More over, mechanisms underlying epigenetic changes in plants have not yet been determined since most reports showed only the level or/and distribution of DNA methylation and histone modifications. Various epigenetic mechanisms are involved in response to abiotic stressors, and several of them are still unknown. Integrated analysis of the changes in the genome by omic approaches should help to identify novel components underlying mechanisms involved in DNA methylation and histone modifications associated with plant response to environmental stressors.

Arabidopsis VIM Proteins Regulate Epigenetic Silencing by Modulating DNA Methylation and Histone Modification in Cooperation with MET1

CUT&Tag-BS for simultaneous profiling of histone modification and DNA methylation with high efficiency and low cost

Simple SummaryEpigenetic modifications, such as DNA methylation and histone modification, have been found to alter in various cancer types. These modifications lead to uncontrolled cellular proliferation, evasion from apoptosis, and metastasis. Deregulation in epigenetic pathways often results in the suppression of tumor-suppression genes or activation of oncogenes in cancers. Inhibitors targeting deregulated enzymes can restore balance by reactivating altered pathways. Several inhibitors that target DNA methylation and histone modifications are currently being used in clinics and have shown promising results in cancer therapeutics.The three-dimensional architecture of genomes is complex. It is organized as fibers, loops, and domains that form high-order structures. By using different chromosome conformation techniques, the complex relationship between transcription and genome organization in the three-dimensional organization of genomes has been deciphered. Epigenetic changes, such as DNA methylation and histone modification, are the hallmark of cancers. Tumor initiation, progression, and metastasis are linked to these epigenetic modifications. Epigenetic inhibitors can reverse these altered modifications. A number of epigenetic inhibitors have been approved by FDA that target DNA methylation and histone modification. This review discusses the techniques involved in studying the three-dimensional organization of genomes, DNA methylation and histone modification, epigenetic deregulation in cancer, and epigenetic therapies targeting the tumor.

Influence of extremely-low-frequency magnetic fields on epigenetic programming and cellular differentiation

Both DNA methylation and histone modification are involved in establishing patterns of gene repression during development. Certain forms of histone methylation cause local formation of heterochromatin, which is readily reversible, whereas DNA methylation leads to stable long-term repression. It has recently become apparent that DNA methylation and histone modification pathways can be dependent on one another, and that this crosstalk can be mediated by biochemical interactions between SET domain histone methyltransferases and DNA methyltransferases. Relationships between DNA methylation and histone modification have implications for understanding normal development as well as somatic cell reprogramming and tumorigenesis.

The interplay between histone modifications and DNA methylation drives the establishment and maintenance of the cellular epigenomic landscape, but it remains challenging to investigate the complex relationship between these epigenetic marks across the genome. Here we describe a nanopore-sequencing-based-method, nanoHiMe-seq, for interrogating the genome-wide localization of histone modifications and DNA methylation from single DNA molecules. nanoHiMe-seq leverages a nonspecific methyltransferase to exogenously label adenine bases proximal to antibody-targeted modified nucleosomes in situ. The labelled adenines and the endogenous methylated CpG sites are simultaneously detected on individual nanopore reads using a hidden Markov model, which is implemented in the nanoHiMe software package. We demonstrate the utility, robustness and sensitivity of nanoHiMe-seq by jointly profiling DNA methylation and histone modifications at low coverage depths, concurrently determining phased patterns of DNA methylation and histone modifications, and probing the intrinsic connectivity between these epigenetic marks across the genome.

Update on epigenetics in allergic disease

Epigenetics refers to functionally relevant genomic changes that do not involve changes in the basic nucleotide sequence. Majorly, these are of two types: DNA methylation and histone modifications. Small RNA molecules called miRNAs are often thought to mediate post-transcriptional epigenetic changes by mRNA degradation or translational attenuation. While DNA methylation and histone modifications have their own independent effects on various cellular events, several reports are suggestive of an obvious interplay between these phenomena and the miRNA regulatory program within the cell. Several miRNAs like miR-375, members of miR-29 family, miR-34, miR-200, and others are regulated by DNA methylation and histone modifications in various types of cancers and metabolic diseases. On the other hand, miRNAs like miR-449a, miR-148, miR-101, miR-214, and miR-128 target members of the epigenetic machinery and their dysregulation leads to diverse cellular aberrations. In spite of being independent cellular events, emergence of such reports that suggest a connection between DNA methylation, histone modification, and miRNA function in several diseases indicate that this connecting axis offers a valuable target with great therapeutic potential that might be exploited for disease management. We review the current status of crosstalk between the major epigenetic modifications and the miRNA machinery and discuss this in the context of health and disease.

Epigenetic flexibility in metabolic regulation: disease cause and prevention?

DNA methylation and histone modifications are crucial epigenetic modifications that involved in transcriptional regulatory network. Due to environmental cues, distortion in epigenomic landscape—in DNA methylation and histone modification—might be considered as a reason for aberrant gene expression in cancer. A confounding puzzle in cancer epigenetics is to decipher whether a significant mechanism between DNA methylation and histone modification triggers tumorigenesis initiation and progression. ChIP-BS-seq is a technique that combines chromatin immunoprecipitation and bisulfite conversion followed by high-throughput sequencing to study genome-wide cross talk between DNA methylation and histone modification. In this chapter, we have explored background, technological advancement in epigenomics research and its future developments. We also have summarized our latest findings on using ChIP-BS-seq in cancer cell lines.

New advances of DNA methylation and histone modifications in rheumatoid arthritis, with special emphasis on MeCP2