5-hydroxymethylcytosine (5hmc): an epigenetic modification of DNA; can result from the oxidation of 5-methylcytosine modification by the Tet family of enzymes.

5-methylcytosine (5mC): an epigenetic modification of DNA that usually occurs at CpG dinucleotides; the 5mC modification usually correlates with repressed gene expression.

Adult stem cell: multipotent stem cells present in differentiated tissue; also known as tissue-specific stem cells.

Bisulfite conversion: the deamination of non-methylated cytosine bases to uracil by treatment with sodium bisulfite (NaHSO3); 5mC bases are resistant to bisulfite conversion.

Bisulfite sequencing: determining the sequence of bisulfite-converted DNA; considered the “gold standard” of DNA methylation analysis.

Blastocyst: an early embryonic structure consisting of distinct outer trophectoderm cells, which develop into the placenta, and the inner cell mass, which develops into the fetus.

Body methylation: methylation of DNA bases within coding sequences of actively transcribed genes found within euchromatin.

Bromodomain: a protein motif that binds acetylated lysine residues; commonly present in proteins that recognize acetylated histones, such as chromatin-remodeling factors.

ChIP-on-chip: a combination of chromatin immunoprecipitation and DNA hybridization to genomic microarrays (also known as ChIP-chip).

ChIP-Seq: a method combining chromatin immunoprecipitation and DNA sequencing to analyze specific DNA-protein interactions. Next-gen DNA sequencing is often performed, resulting in a genome-wide analysis of protein-chromatin interactions.

Chromatin: the complex of DNA, histones, RNA, and other proteins that comprise the structural basis of chromosomes.

Chromatin immunoprecipitation (ChIP): a method used to identify proteins bound to DNA and the sequence to which they bind using an antibody to specifically immunoprecipitate the protein of interest; the DNA sequence that co-precipitates with the protein can be identified by PCR, hybridization, or sequencing.

Chromodomain: a motif of 40-50 amino acids common to proteins that function in chromatin remodeling; may function in binding DNA, RNA, and protein; often binds methylated histones.

Combined Bisulfite Restriction Analysis (COBRA): a quantitative technique for the detection of methylated DNA in which DNA is subjected to bisulfite conversion and digestion with restriction endonucleases that are specific for sequences containing CpG sites (and thus are subject to methylation); the digestion products are a direct reflection of DNA methylation at the restriction sites.

Constitutive heterochromatin: heterochromatin, often located near centromeres (also known as pericentric heterochromatin), that is irreversibly silenced; DNA within constitutive heterochromatin is typically AT-rich.

CpG islands: regions of DNA enriched for CG dinucleotides; CpG islands are typically 300-3000 bp long, located upstream of gene coding regions, and usually protected from DNA methylation.

De novo methylation: the establishment of genomic DNA methylation during embryonic development; in mammals, after genomic DNA is demethylated in the zygote, the methyltransferases Dnmt3a and Dnmt3b methylate DNA between embryonic implantation and gastrulation.

Differentially DNA-Methylated Region (DMR): a region of DNA that is methylated differentially in the two chromosomes of a diploid cell; often associated with genomic imprinting.

DNA methylation: a heritable, reversible epigenetic modification in which a methyl group is covalently added to a DNA sequence, usually the 5th carbon of the cytosine pyrimidine ring in a CpG dinucleotide, although CpHpG and CpHpH sequences can be methylated in plants.

DNA methyltransferase: an enzyme that catalyzes the addition of a methyl group to a DNA nitrogenous base; the 5mC class adds a methyl group to the 5-carbon position of cytosine bases; humans produce DNMT1, the maintenance methyltransferase, which is active at hemimethylated sites, and the methyltransferases DNMT3a and DNMT3b, which function during embryonic development and shortly after birth.

Dosage compensation: mechanisms involved in equalizing the expression of genes encoded on the X-chromosome between the two sexes; some examples are X chromosome inactivation in female mammals, X chromosome upregulation in male Drosophila flies, and partial repression of both X chromosomes in hermaphrodite C. elegans worms.

Embryo: an individual organism between the onset of multicellularity through birth; alternatively defined as beginning with implantation of the blastocyst in the uterus; in human development the term is usually used until the 8th week of pregnancy, from which point the term fetus is used.

Embryonic stem cell (ES cell): pluripotent stem cells found in the blastocyst, inner cell mass, and embryo.

Epiallele: variations in the epigenetic status of a gene or locus; often associated with differential methylation.

Epigenetic mark: a modifying moiety that carries an epigenetic signal; examples include methylation of DNA, methylation, acetylation, phosphorylation, ubiquitination, and sumoylation of histones.

Epigenetic silencing: the suppression of gene transcription or expression because of epigenetic factors such as RNAi, DNA methylation, histone modification, or chromatin remodeling.

Epigenetic therapy: application of chemical compounds, such as DNA methyltransferase inhibitors (e.g. 5-azacytidine, 5-aza-2’-deoxycytidine), to target epigenetically regulated mechanisms in patients.

Epigenetics: heritable traits that can be maintained through cell division and sexual reproduction that are not the result of a change in DNA sequence; epigenetic factors include chromatin conformation, DNA methylation, histone modification, and RNAi.

Epigenome: all of the epigenetic marks present throughout the genome of a cell.

Euchromatin: decondensed chromatin that is conformationally favorable for transcription; euchromatin typically has less DNA methylation than heterochromatin, and its associated histones have modifications that favor gene transcription.

Facultative heterochromatin: heterochromatin that may become transcriptionally active in specific cell development fates.

Hemimethylated: the status of a symmetrical DNA sequence (such as CG or CHG) that is methylated on only one strand.

Heterochromatin: condensed chromatin that is conformationally unfavorable for transcription; heterochromatin typically has more DNA methylation than euchromatin, is associated with histones containing repressive modifications, and can be associated with repressive non-coding RNAs.

Histone acetyltransferase (HAT): enzyme that acetylates histones at specific lysine residues.

Histone deacetylase (HDAC): enzyme that remove acetyl groups from N(6)-acetyl-lysine residues on a histone.

Histone: chromosomal architectural proteins that bind DNA within nucleosomes; in eukaryotes there are 4 core histones, H2A, H2B, H3, and H4, the non-nucleosomal linker histone H1, and variant histones.

Histone code: the hypothesis that the locations and types of histone modifications, through chromatin remodeling and/or recruitment of transcription factors, predicts the effects of those modifications on gene expression.

Histone methyltransferase: a class of enzymes that add methyl groups to specific histone residues; members include histone-lysine N-methyltransferase and histone-arginine N-methyltransferase.

Histone modification: posttranslational addition or removal of epigenetic marks from histones; includes methylation, acetylation, phosphorylation, ubiquitination, sumoylation, and the removal of these marks.

Histone variants: paralogous histones that can replace the major core histone proteins and may have distinct gene regulatory functions; also known as replacement histones.

Hypermethylation: increase in the level of DNA methylation in a population of cells relative to a reference or normal sample; may be used to describe a specific nucleotide or a group of nucleotides.

Hypomethylation: decrease in the level of DNA methylation in a population of cells relative to a reference or normal sample; may be used to describe a specific nucleotide or a group of nucleotides.

Imprinting: epigenetic regulation in which maternally and paternally inherited alleles are differentially expressed owing to cis-acting modifications of DNA or histones inherited from parental chromosomes.

Inner cell mass (ICM): pluripotent cells located in the interior of the blastocyst that develop into the fetus.

Induced Pluripotent Stem (iPS) Cells: differentiated cells reprogrammed to pluripotency by ectopic expression of reprogramming factors such as Oct3/4, Sox2, Klf4, and c-Myc.

Large non-coding RNA: non-coding RNA larger than 200 nucleotides; can have roles in epigenetic regulation of gene expression

Loss of imprinting (LOI): activation of an allele normally silenced by genomic imprinting; LOI causes excess gene product to be produced and is often associated with tumorigenesis.

Methylation sensitive PCR (MSP): a technique used to determine the methylation status of specific DNA sequences by PCR amplification of a bisulfite-converted template with different primer sets that distinguish methylated DNA and non-methylated (C?T converted) DNA.

Methylated DNA Immunoprecipitation (Methyl-DIP or MeDIP): a technique used to identify methylated DNA by precipitation with an antibody specific for 5mC and followed by detection of precipitated DNA by PCR, hybridization to a genomic microarray, or sequencing.

Methylation-sensitive Single-Nucleotide Primer Extension (Ms-SNuPE): a technique used to query methylation status of a targeted base bisulfite conversion followed by primer extension with labeled dCTP or dTTP to distinguish methylated and non-methylated DNA.

microRNA (miRNA): Small RNA molecules (usually 21-23 nulceotides) that play a role in regulating gene expression by transiently suppressing translation of an mRNA molecule or by directing its cleavage.

Multipotency: the property of stem cells describing their ability to differentiate into cells of a specific lineage, but not other lineages; example: hematopoietic stem cells can differentiate into multiple types of blood cells, but not into muscle cells, skin cells, or cells of any other lineage.

Non-coding RNA (ncRNA): RNA molecules that do not contain protein-coding potential; ncRNAs can be highly abundant and functionally important RNA molecules that can epigenetically regulated gene expression or other cellular processes, such as nuclear organization and splicing; the majority of most genomes are transcribed as non-coding RNA; examples include microRNAs (miRNAs), small interfering RNAs (siRNAs), Piwi-interacting RNAs (piRNAs), large non-coding RNAs (lncRNAs), natural antisense transcripts (NATs) and large intergenic RNAs (lincRNAs).

Nucleosome: the repeating unit of chromatin structure; one nucleosome is comprised of 147 bp of DNA wrapped around a protein octamer including two molecules each of the core histones H2A,histone H2B, histone H3, and histone H4.

Piwi-interacting RNA (piRNA): the largest class of small non-coding RNA molecules expressed in animal cells; piRNAs are 26-34 nucleotides in length and form RNA-protein complexes through interactions with piwi proteins; piRNAs differ from miRNAs and siRNA in both methods of biogenesis and function, but are known to play a role in silencing retrotransposons in germ cells.

Pluripotency: the property of embryonic stem cells to differentiate into cells of any three germ layers (endoderm, mesoderm, ectoderm); pluripotent cells are more differentiated than totipotent cells and less differentiated than multipotent cells.

Polycomb-group (PcG): a group of proteins functioning in histone modification, histone binding, or DNA binding that facilitate gene repression; named for the Drosophila melanogaster Polycomb gene.

Position effect variegation (PEV): the variable silencing of a gene because of its proximity to heterochromatin.

RNA interference (RNAi ): posttranscriptional gene silencing mediated by small RNA sequences that are capable of hybridizing to a target mRNA sequences.

Small activating RNA (saRNA): miRNAs that can activate gene expression by binding to promoter sequences.

Small interfering RNAs (siRNA): small RNAs (21-24 nt) that function in gene silencing, heterochromatin assembly, and RNA directed DNA methylation.

Somatic cell nuclear transfer (SCNT): transplantation of a diploid nucleus from a somatic cell to an enucleated egg cell, artificially mimicking fertilization and potentiating development; SCNT is used for reproductive cloning.

Stem cell: an undifferentiated cell that is capable of producing daughter stem cells by mitosis or differentiating into specialized cell types.

Totipotency: the property of fertilized egg cells and early zygotic cells to differentiate into embryonic and extraembryonic cells.

Trithorax-group (trxG): a group of proteins functioning in transcriptional regulation, chromatin remodeling, and histone lysine methyltransferase activity that facilitate gene expression; named for the Drosophila melanogaster trithorax gene.

Tumor suppressor gene: a gene that functions in regulation of cell cycle and/or promotes apoptosis, protecting the individual from the development of cancer; tumor suppressor genes are often mutated in cancer.

Uniparental disomy: the condition in which an offspring inherits both copies of a chromosome (or a segment thereof) from the same parent. Genomic imprinting under such conditions can cause loss of expression or aberrant expression of alleles.

X-inactivation: a dosage compensation mechanism in which one of two X-chromosomes in the cells of female mammals is epigenetically silenced.

Xist: X inactive specific transcript; the non-coding RNA transcribed from the X-inactivation center (Xic) that binds along the entire chromosome from which it is transcribed to mediate X chromosome inactivation in placental mammals.

Zygote: the totipotent cell that results from the union of the oocyte and sperm gametes.