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