• CpG
• DNA methylation
• DNMT1
• DNMT5
• H3K9 methylation
• histones

• Humans
• Chromatin/genetics
• Chromatin/metabolism
• Epigenesis, Genetic
• DNA Methylation
• Animals
• Histones/metabolism
• Histones/genetics
• CpG Islands/genetics
• Nucleosomes/metabolism
• Saccharomyces cerevisiae/genetics

• DNA methylation
• aging
• cancer
• epigenetics
• gene regulation
• mitosis

• Humans
• DNA Methylation/genetics
• Epigenesis, Genetic
• Mitosis/genetics
• Mutation
• Neoplasms/genetics
• Neoplasms/pathology
• Animals
• DNA Replication/genetics

• R35 GM146978 NIGMS NIH HHS

• DNA methylation
• advanced paternal age
• age
• assisted reproductive technologies
• delayed parenthood
• epigenetic clock
• epigenetics
• non-coding RNA
• pregnancy success
• sperm

The observed risk of autoimmune hepatitis exceeds its genetic risk, and epigenetic factors that alter gene expression without changing nucleotide sequence may help explain the disparity. Key objectives of this review are to describe the epigenetic modifications that affect gene expression, discuss how they can affect autoimmune hepatitis, and indicate prospects for improved management. Multiple hypo-methylated genes have been described in the CD4⁺ and CD19⁺ T lymphocytes of patients with autoimmune hepatitis, and the circulating micro-ribonucleic acids, miR-21 and miR-122, have correlated with laboratory and histological features of liver inflammation. Both epigenetic agents have also correlated inversely with the stage of liver fibrosis. The reduced hepatic concentration of miR-122 in cirrhosis suggests that its deficiency may de-repress the pro-fibrotic prolyl-4-hydroxylase subunit alpha-1 gene. Conversely, miR-155 is over-expressed in the liver tissue of patients with autoimmune hepatitis, and it may signify active immune-mediated liver injury. Different epigenetic findings have been described in diverse autoimmune and non-autoimmune liver diseases, and these changes may have disease-specificity. They may also be responses to environmental cues or heritable adaptations that distinguish the diseases. Advances in epigenetic editing and methods for blocking micro-ribonucleic acids have improved opportunities to prove causality and develop site-specific, therapeutic interventions. In conclusion, the role of epigenetics in affecting the risk, clinical phenotype, and outcome of autoimmune hepatitis is under-evaluated. Full definition of the epigenome of autoimmune hepatitis promises to enhance understanding of pathogenic mechanisms and satisfy the unmet clinical need to improve therapy for refractory disease.

• Epigenesis, Genetic
• Fibrosis
• Hepatitis, Autoimmune
• Humans
• Liver Cirrhosis/metabolism
• MicroRNAs/genetics
• MicroRNAs/therapeutic use

• DNA methylation
• Diet
• Intestines
• Nutritional status

• DNA methylation
• Epigenetics
• Histone methylation
• Intergenerational
• Non-Mendellian
• Non-genetic
• Small RNAs
• Transgenerational epigenetic inheritance

• Cancer
• Cancer immunotherapy
• Clinical pharmacology
• DNA-methylation
• Epigenetics
• Nanobiomedicine

Kaposi's sarcoma (KS), is an AIDS-associated neoplasm caused by the KS herpesvirus (KSHV/ HHV-8). KSHV-induced sarcomagenesis is the consequence of oncogenic viral gene expression as well as host genetic and epigenetic alterations. Although KSHV is found in all KS-lesions, the percentage of KSHV-infected (LANA+) spindle-cells of the lesion is variable, suggesting the existence of KS-spindle cells that have lost KSHV and proliferate autonomously or via paracrine mechanisms. A mouse model of KSHVBac36-driven tumorigenesis allowed us to induce KSHV-episome loss before and after tumor development. Although infected cells that lose the KSHV-episome prior to tumor formation lose their tumorigenicity, explanted tumor cells that lost the KSHV-episome remained tumorigenic. This pointed to the existence of virally-induced irreversible oncogenic alterations occurring during KSHV tumorigenesis supporting the possibility of hit and run viral-sarcomagenesis. RNA-sequencing and CpG-methylation analysis were performed on KSHV-positive and KSHV-negative tumors that developed following KSHV-episome loss from explanted tumor cells. When KSHV-positive cells form KSHV-driven tumors, along with viral-gene upregulation there is a tendency for hypo-methylation in genes from oncogenic and differentiation pathways. In contrast, KSHV-negative tumors formed after KSHV-episome loss, show a tendency towards gene hyper-methylation when compared to KSHV-positive tumors. Regarding occurrence of host-mutations, we found the same set of innate-immunity related mutations undetected in KSHV-infected cells but present in all KSHV-positive tumors occurring en exactly the same position, indicating that pre-existing host mutations that provide an in vivo growth advantage are clonally-selected and contribute to KSHV-tumorigenesis. In addition, KSHV-negative tumors display de novo mutations related to cell proliferation that, together with the PDGFRAD842V and other proposed mechanism, could be responsible for driving tumorigenesis in the absence of KSHV-episomes. KSHV-induced irreversible genetic and epigenetic oncogenic alterations support the possibility of “hit and run” KSHV-sarcomagenesis and point to the existence of selectable KSHV-induced host mutations that may impact AIDS-KS treatment.

KSHV-infected KS lesions are composed of latently-infected cells, as well as cells expressing lytic genes that have been implicated in the development of the KS angioproliferative phenotype. The existence of KS lesions with varying levels of KSHV-infected cells suggests also the existence of virus-independent “hit and run” mechanisms of sarcomagenesis, whereby viral infection irreversibly induce genetic or epigenetic oncogenic alterations in host cells. We used the unique mECK36 animal model of multistep KSHV sarcomagenesis to dissect transcriptional, genetic and epigenetic mechanisms of KSHV dependent tumorigenesis and during tumorigenesis following KSHV-episome loss (“hit and run”) sarcomagenesis in an unbiased high-throughput fashion. These analyses revealed that KSHV in vivo tumorigenesis: A) Occurs predominantly with CpG hypo-methylation of oncogenic and differentiation pathways. B) Selects for pre-existing host mutations that allow the KSHV oncovirus to express oncogenic lytic genes by creating permissive environment for viral-induced innate immunity and inflammation, which provides a selective advantage in vivo conducive to tumorigenesis. Our results highlight the mutagenic potential of KSHV pointing to the existence in KS lesions, of KSHV-induced oncogenic host mutations that could be selected upon treatment and impact AIDS-KS therapies.

• Animals
• Cell Line
• Cell Transformation, Viral
• DNA Methylation
• Gene Expression Regulation, Neoplastic
• Gene Expression Regulation, Viral
• Herpesvirus 8, Human/genetics
• Herpesvirus 8, Human/metabolism
• High-Throughput Nucleotide Sequencing
• Mice
• Neoplasms, Experimental/genetics
• Neoplasms, Experimental/metabolism
• Neoplasms, Experimental/pathology
• Neoplasms, Experimental/virology
• Plasmids/genetics
• Plasmids/metabolism
• Sarcoma, Kaposi/genetics
• Sarcoma, Kaposi/metabolism
• Sarcoma, Kaposi/pathology
• Sarcoma, Kaposi/virology

• P30 AI073961 NIAID NIH HHS
• R01 CA136387 NCI NIH HHS
• U54 CA221208 NCI NIH HHS
• Israel Science Foundation
• Israel Cancer Research Fund
• National Institutes of Health
• National Cancer Institute

• DNA methylation
• gene silencing
• protein O-glycosylation

• Acetylglucosamine/metabolism
• Animals
• Chromatin/metabolism
• DNA (Cytosine-5-)-Methyltransferase 1/genetics
• DNA (Cytosine-5-)-Methyltransferase 1/metabolism
• DNA Methylation
• Epigenesis, Genetic
• Gene Silencing
• Glycosylation
• Humans
• Methylation
• N-Acetylglucosaminyltransferases
• Nuclear Proteins/metabolism
• Promoter Regions, Genetic
• Protein Processing, Post-Translational
• Proteomics
• Repressor Proteins/metabolism
• Retroelements/physiology
• Transcription Factors/metabolism
• Tripartite Motif-Containing Protein 28/metabolism

• R21 HG009187 NHGRI NIH HHS

• Aging
• DNA methylation
• Epigenetic age
• Epigenetic clock
• Epigenetic reprogramming

The heavily methylated vertebrate genomes are punctuated by stretches of poorly methylated DNA sequences that usually mark gene regulatory regions. It is known that the methylation state of these regions confers transcriptional control over their associated genes. Given its governance on the transcriptome, cellular functions and identity, genome-wide DNA methylation pattern is tightly regulated and evidently predefined. However, how is the methylation pattern determined in vivo remains enigmatic. Based on in silico and in vitro evidence, recent studies proposed that the regional hypomethylated state is primarily determined by local DNA sequence, e.g., high CpG density and presence of specific transcription factor binding sites. Nonetheless, the dependency of DNA methylation on nucleotide sequence has not been carefully validated in vertebrates in vivo. Herein, with the use of medaka (Oryzias latipes) as a model, the sequence dependency of DNA methylation was intensively tested in vivo. Our statistical modeling confirmed the strong statistical association between nucleotide sequence pattern and methylation state in the medaka genome. However, by manipulating the methylation state of a number of genomic sequences and reintegrating them into medaka embryos, we demonstrated that artificially conferred DNA methylation states were predominantly and robustly maintained in vivo, regardless of their sequences and endogenous states. This feature was also observed in the medaka transgene that had passed across generations. Thus, despite the observed statistical association, nucleotide sequence was unable to autonomously determine its own methylation state in medaka in vivo. Our results apparently argue against the notion of the governance on the DNA methylation by nucleotide sequence, but instead suggest the involvement of other epigenetic factors in defining and maintaining the DNA methylation landscape. Further investigation in other vertebrate models in vivo will be needed for the generalization of our observations made in medaka.

The genomes of vertebrate animals are naturally and extensively modified by methylation. The DNA methylation is essential to normal functions of cells, hence the whole animal, since it governs gene expression. Defects in the establishment and maintenance of proper methylation pattern are commonly associated with various developmental abnormalities and diseases. How exactly is the normal pattern defined in vertebrate animals is not fully understood, but recent researches with computational analyses and cultured cells suggested that DNA sequence is a primary determinant of the methylation pattern. This study encompasses the first experiments that rigorously test this notion in whole animal (medaka fish). In statistical sense, we observed the very strong correlation between DNA sequence and methylation state. However, by introducing unmethylated and artificially methylated native genomic DNA sequences into the genome, we demonstrated that the artificially conferred methylation states were robustly maintained in the animal, independent of the sequence and native state. Our results thus demonstrate that genome-wide DNA methylation pattern is not autonomously determined by the DNA sequence, which underpins the vital role of DNA methylation pattern as a core epigenetic element.

• Aging
• DNA methylation
• Epigenetic age
• Epigenetic reprogramming
• Epigenetics
• Histone modification
• miRNA

The prevailing views as to the form, function, and regulation of genomic methylation patterns have their origin many years in the past, at a time when the structure of the mammalian genome was only dimly perceived, when the number of protein-encoding mammalian genes was believed to be at least five times greater than the actual number, and when it was not understood that only ~10% of the genome is under selective pressure and likely to have biological function. We use more recent findings from genome biology and whole-genome methylation profiling to provide a reappraisal of the shape of genomic methylation patterns and the nature of the changes that they undergo during gametogenesis and early development. We observe that the sequences that undergo deep changes in methylation status during early development are largely sequences without regulatory function. We also discuss recent findings that begin to explain the remarkable fidelity of maintenance methylation. Rather than a general overview of DNA methylation in mammals (which has been the subject of many reviews), we present a new analysis of the distribution of methylated CpG dinucleotides across the multiple sequence compartments that make up the mammalian genome, and we offer an updated interpretation of the nature of the changes in methylation patterns that occur in germ cells and early embryos. We discuss the cues that might designate specific sequences for demethylation or de novo methylation during development, and we summarize recent findings on mechanisms that maintain methylation patterns in mammalian genomes. We also describe the several human disorders, each very different from the other, that are caused by mutations in DNA methyltransferase genes.

• DNA cytosine methylation
• Epigenetics
• Mammalian DNA methyltransferases
• Methylation dynamics
• Methylation-related human diseases

• Chromatin organization
• cell cycle
• epigenetic memory
• epigenetics
• histone modification
• mitosis
• mitotic bookmarking

• Animals
• Cell Differentiation
• Chromatin/genetics
• Chromosomes/genetics
• Epigenesis, Genetic
• Histone Code
• Histones/genetics
• Humans
• Mitosis

• R01 GM112720 NIGMS NIH HHS
• U54 DK107980 NIDDK NIH HHS
• R01 AI117839 NIAID NIH HHS
• U01 DA040588 NIDA NIH HHS
• U54 HG007010 NHGRI NIH HHS
• R01 HG003143 NHGRI NIH HHS
• U01 HG007910 NHGRI NIH HHS
• U54 CA193419 NCI NIH HHS
• Howard Hughes Medical Institute

• Biomedical Research
• Epigenesis, Genetic
• Epigenomics/methods
• Genetic Predisposition to Disease
• Humans
• Inflammatory Bowel Diseases/genetics
• Inflammatory Bowel Diseases/microbiology
• Microbiota

Adjacent CpG sites in mammalian genomes can be co-methylated due to the processivity of methyltransferases or demethylases. Yet discordant methylation patterns have also been observed, and found related to stochastic or uncoordinated molecular processes. We focused on a systematic search and investigation of regions in the full human genome that exhibit highly coordinated methylation. We defined 147,888 blocks of tightly coupled CpG sites, called methylation haplotype blocks (MHBs) with 61 sets of whole genome bisulfite sequencing (WGBS) data, and further validated with 101 sets of reduced representation bisulfite sequencing (RRBS) data and 637 sets of methylation array data. Using a metric called methylation haplotype load (MHL), we performed tissue-specific methylation analysis at the block level. Subsets of informative blocks were further identified for deconvolution of heterogeneous samples. Finally, we demonstrated quantitative estimation of tumor load and tissue-of-origin mapping in the circulating cell-free DNA of 59 cancer patients using methylation haplotypes.

• DNA (Cytosine-5-)-Methyltransferases/metabolism
• DNA Methylation
• Epigenesis, Genetic
• Lab-On-A-Chip Devices

• Cardiovascular Diseases/epidemiology
• Cardiovascular Diseases/etiology
• Cardiovascular Diseases/prevention & control
• DNA Methylation
• Epigenesis, Genetic/genetics
• Folic Acid Deficiency/complications
• Gene Expression/genetics
• Gene Silencing
• Genetic Predisposition to Disease/genetics
• Genotype
• Holistic Health
• Humans
• Hyperhomocysteinemia/complications
• Infections/complications
• Iron Overload/complications
• Phenotype
• Risk Factors

• DNA methylation
• aging
• cell differentiation
• enhancer regulation
• lineage commitment

• Animals
• Cell Differentiation
• Cell Lineage/genetics
• DNA Methylation
• Epigenesis, Genetic
• Gene Expression Regulation, Developmental
• Humans
• Mammals/genetics

Alzheimer’s disease (AD) is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when therapeutic strategies have become unviable. Although several genetic alterations have been associated with AD, the vast majority of AD cases do not show strong genetic underpinnings and are thus considered a consequence of non-genetic factors. Epigenetic mechanisms allow for the integration of long-lasting non-genetic inputs on specific genetic backgrounds, and recently, a growing number of epigenetic alterations in AD have been described. For instance, an accumulation of dysregulated epigenetic mechanisms in aging, the predominant risk factor of AD, might facilitate the onset of the disease. Likewise, mutations in several enzymes of the epigenetic machinery have been associated with neurodegenerative processes that are altered in AD such as impaired learning and memory formation. Genome-wide and locus-specific epigenetic alterations have also been reported, and several epigenetically dysregulated genes validated by independent groups. From these studies, a picture emerges of AD as being associated with DNA hypermethylation and histone deacetylation, suggesting a general repressed chromatin state and epigenetically reduced plasticity in AD. Here we review these recent findings and discuss several technical and methodological considerations that are imperative for their correct interpretation. We also pay particular focus on potential implementations and theoretical frameworks that we expect will help to better direct future studies aimed to unravel the epigenetic participation in AD.

• Alzheimer’s disease
• DNA methylation
• epigenetics
• histone acetylation
• histone methylation
• histone phosphorylation
• neuroepigenetics

Cells require nucleotides to support DNA replication and to repair damaged DNA. In addition to de novo synthesis, cells recycle nucleotides from the DNA of dying cells or from cellular material ingested through the diet. Salvaged nucleosides come with the complication that they can contain epigenetic modifications. Since epigenetic inheritance of DNA methylation mainly relies on copying of the modification pattern from parental strands^1-3, random incorporation of pre-modified bases during replication could have profound implications for epigenome fidelity and yield adverse cellular phenotypes. Although the salvage mechanism of 5-methyl-2′deoxycytidine (5mdC) has been investigated before^4-6, currently it remains unknown how cells deal with the recently identified oxidised forms of 5mdC – 5-hydroxymethyl-2′deoxycytidine (5hmdC), 5-formy-2′deoxycytidine (5fdC) and 5-carboxyl-2′deoxycytidine (5cadC)^7-10. Here we demonstrate that enzymes of the nucleotide salvage pathway display substrate selectivity, effectively protecting newly synthesized DNA from the incorporation of epigenetically modified forms of cytosine. Thus cell lines and animals can tolerate high doses of these modified cytidines without any deleterious effects on physiology. Interestingly, by screening cancer cell lines for growth defects following exposure to 5hmdC, we unexpectedly identify a subset of cell lines where 5hmdC or 5fdC administration leads to cell lethality. Using genomic approaches we discover that the susceptible cell lines overexpress cytidine deaminase (CDA). CDA converts 5hmdC and 5fdC into variants of uridine that are incorporated into DNA, resulting in accumulation of DNA damage and ultimately, cell death. Our observations extend current knowledge of the nucleotide salvage pathway by revealing the metabolism of oxidised epigenetic bases, and suggest a therapeutic option for cancers, such as pancreatic cancer, that have CDA overexpression and are resistant to treatment with other cytidine analogues¹¹.

• DNA demethylation
• DNA methylation
• chromatin
• epigenetics

It is thought that methylcytosine can be inherited through meiosis and mitosis, and that epigenetic variation may be under genetic control or correlation may be caused by neutral drift. However, DNA methylation also varies with tissue, developmental stage, and environmental factors. Eliminating these factors, we analyzed the levels and patterns, diversity and structure of genomic methylcytosine in the xylem of nine natural populations of Chinese white poplar.

On average, the relative total methylation and non-methylation levels were approximately 26.567% and 42.708% (P<0.001), respectively. Also, the relative CNG methylation level was higher than the relative CG methylation level. The relative methylation/non-methylation levels were significantly different among the nine natural populations. Epigenetic diversity ranged from 0.811 (Gansu) to 1.211 (Shaanxi), and the coefficients of epigenetic differentiation (G_ST = 0.159) were assessed by Shannon’s diversity index. Co-inertia analysis indicated that methylation-sensitive polymorphism (MSP) and genomic methylation pattern (CG-CNG) profiles gave similar distributions. Using a between-group eigen analysis, we found that the Hebei and Shanxi populations were independent of each other, but the Henan population intersected with the other populations, to some degree.

Genome methylation in Populus tomentosa presented tissue-specific characteristics and the relative 5′-CCGG methylation level was higher in xylem than in leaves. Meanwhile, the genome methylation in the xylem shows great epigenetic variation and could be fixed and inherited though mitosis. Compared to genetic structure, data suggest that epigenetic and genetic variation do not completely match.

• Base Sequence
• China
• DNA Methylation/genetics
• Epigenesis, Genetic
• Genetic Variation
• Genome, Plant/genetics
• Polymerase Chain Reaction
• Polymorphism, Genetic
• Populus/genetics
• Principal Component Analysis

• 5-Methylcytosine/analysis
• Animals
• Cytosine/analogs & derivatives
• Cytosine/analysis
• Embryonic Stem Cells/metabolism
• Epigenomics
• Gene Expression Regulation
• Genome, Human
• Genome-Wide Association Study
• Humans
• Mice
• Sequence Analysis, DNA/methods

• K01 HG006699 NHGRI NIH HHS
• R01 GM071440 NIGMS NIH HHS
• NS051630 NINDS NIH HHS
• P50 AG025688 NIA NIH HHS
• R01 NS051630 NINDS NIH HHS
• U01 ES017166 NIEHS NIH HHS
• R21 NS067461 NINDS NIH HHS
• GM071440 NIGMS NIH HHS
• U01ES017166 NIEHS NIH HHS
• R56 MH076090 NIMH NIH HHS
• R01 MH076090 NIMH NIH HHS
• P50AG025688 NIA NIH HHS

Genomic DNA methylation contributes substantively to transcriptional regulations that underlie mammalian development and cellular differentiation. Much effort has been made to decipher the molecular mechanisms governing the establishment and maintenance of DNA methylation patterns. However, little is known about genome-wide variation of DNA methylation patterns. In this study, we introduced the concept of methylation entropy, a measure of the randomness of DNA methylation patterns in a cell population, and exploited it to assess the variability in DNA methylation patterns of Alu repeats and promoters. A few interesting observations were made: (i) within a cell population, methylation entropy varies among genomic loci; (ii) among cell populations, the methylation entropies of most genomic loci remain constant; (iii) compared to normal tissue controls, some tumors exhibit greater methylation entropies; (iv) Alu elements with high methylation entropy are associated with high GC content but depletion of CpG dinucleotides and (v) Alu elements in the intronic regions or far from CpG islands are associated with low methylation entropy. We further identified 12 putative allelic-specific methylated genomic loci, including four Alu elements and eight promoters. Lastly, using subcloned normal fibroblast cells, we demonstrated the highly variable methylation patterns are resulted from low fidelity of DNA methylation inheritance.

• Animals
• Cell Division
• Chromatin/chemistry
• Chromatin/genetics
• Chromatin/metabolism
• DNA Methylation
• Epigenesis, Genetic
• Histones/metabolism
• Humans
• Protein Processing, Post-Translational
• RNA, Untranslated/genetics
• RNA, Untranslated/metabolism
• Transcription Factors/metabolism
• Transcription, Genetic

• R01 GM037120 NIGMS NIH HHS
• GM064844 NIGMS NIH HHS
• GM037120 NIGMS NIH HHS
• R37 GM037120 NIGMS NIH HHS
• Howard Hughes Medical Institute
• R01 GM064844 NIGMS NIH HHS

• Animals
• Chromatin/genetics
• Chromatin/metabolism
• DNA Replication
• Epigenesis, Genetic
• Feedback, Physiological
• Histones/metabolism
• Humans
• Models, Genetic
• RNA, Untranslated/genetics
• RNA, Untranslated/metabolism

• R01GM064844 NIGMS NIH HHS
• 4R37GM037120 NIGMS NIH HHS
• R37 GM037120 NIGMS NIH HHS
• Howard Hughes Medical Institute
• R01 GM064844 NIGMS NIH HHS

• dna demethylation
• gadd45
• gadd45a
• gadd45b
• gadd45g
• 5-methylcytosine
• deaminase
• glycosylase
• base excision repair
• nucleotide excision repair

• Animals
• CpG Islands/genetics
• DNA/genetics
• DNA/metabolism
• DNA Methylation
• DNA Repair
• Genome/genetics
• Humans
• Intracellular Signaling Peptides and Proteins/classification
• Intracellular Signaling Peptides and Proteins/metabolism
• GADD45 Proteins

• R01 AG024984 NIA NIH HHS
• AG024984 NIA NIH HHS
• NS048271 NINDS NIH HHS
• R37 NS047344 NINDS NIH HHS
• MH084018 NIMH NIH HHS
• R56 NS047344 NINDS NIH HHS
• R01 NS048271 NINDS NIH HHS
• R01 NS047344 NINDS NIH HHS
• NS047344 NINDS NIH HHS
• P20 MH084018 NIMH NIH HHS

• Ecosystem
• Gene Expression Regulation, Plant
• Plant Development
• Plant Roots/genetics
• Plant Roots/growth & development
• Plants/genetics

• BB/C005120/1 Biotechnology and Biological Sciences Research Council

• Animals
• Azacitidine/administration & dosage
• Azacitidine/pharmacology
• Base Sequence
• Cell Differentiation/drug effects
• Cell Line
• Cell Proliferation/drug effects
• DNA Methylation
• DNA Modification Methylases/antagonists & inhibitors
• DNA Primers/genetics
• Enzyme Inhibitors/administration & dosage
• Enzyme Inhibitors/pharmacology
• Epigenesis, Genetic
• Gene Expression Profiling
• Gene Expression Regulation/drug effects
• Genomic Imprinting
• Histone Deacetylase Inhibitors
• Hydroxamic Acids/administration & dosage
• Hydroxamic Acids/pharmacology
• Mice
• Pluripotent Stem Cells/cytology
• Pluripotent Stem Cells/drug effects
• Pluripotent Stem Cells/enzymology

• Breast/metabolism
• CpG Islands
• DNA Methylation
• DNA Replication
• Epithelial Cells/metabolism
• Humans
• Neoplasms/genetics
• Stomach Neoplasms/genetics