GLOSSARY OF KEY TERMS

Key Terms (A-F)

  • acetylation,  histone acetylation:  the addition of acetyl groups to N-terminal histone tails. 
  • biomarkers: any marker unique to a particular disease or state. Generally in reference to unique sequence changes (genetic biomarker) or epigenetic changes that indicate the presence of disease.    
  • cellular differentiation: the changing of cellular identify overtime. This is generally from a cellular state of more developmental potential to one of less potential.  
  • CG islands: stretches of high GC density and CpG dinucleotides. Often found at promoters, these island sequences are generally unmethylated.    
  • chromatin remodeling, chromatin remodeling complex: the ncorporation, positioning, and removal of nucleosomes, including histone variants, as well as restructuring of histone-DNA interactions using ATP hydrolysis.   
  • condensin: large proteins that participate as a complex to condense, organize, and ultimately separate chromosomes during mitosis.    
  • crispr array locus: a  locus of repeating genetic elements, where foreign DNA has been incorporated for future detection and destruction of invading virus or plasmid using the CRISPR-Cas adaptive immune system.   
  • CRISPR/CAS: clustered  regularly interspaced short palindromic repeat (CRISPR) and the Crispr Associated (CAS) Protein. This is an adaptive immune system in bacteria and archaea, which has been re-purposed for genome editing.    
  • crRNA, gRNA: small RNAs which guide Cas protein to target sequences for digestion. For gene  editing, this in in reference to "guide" RNAs directing Cas protein to a unique DNA coordinate.  
  • ctcf: CCCTC-binding  factor. Often considered an insulating protein, this zinc finger containing  has important roles in controlling the direction of extruding DNA during looping. CTCF is known to bind to the boundaries of topological associated  domains (TADs).   
  • dead cas9 fusions: any fusion to catalytically inactive or "dead" Cas9 protein. For epigenetic engineering, this is generally an epigenetic modifying protein or domain.
  • DNA demethylation: the removal of methyl groups from cytosines. This involves TET and TDG proteins and involves aspect of the DNA excision repair pathways. 
  • dna double-strand break repair: the repair of a DNA double-strand break using a number of  important DNA repair proteins. Can be programmed (meiotic homologous recombination) or by a variety of damaging sources such as ionizing radiation and repair is conducted via 1 of 2 primary repair systems, homologous recombination or non homologous end-joining .
  • DNA DSB, dna double-strand break: the breaking of DNA across both strands of the covalent the sugar-phosphate backbone.    
  • DNA methylation: the addition of methyl groups to DNA. This predominately occurs at CpG dinucleotides using DNA methyltransferase enzymes and co-factor DNA adenosylmethionine (SAM).
  • DNA methylation editing: the addition or removal of select methyl groups to specific  cytosines.
  • DNA methyltransferase: the enzyme type responsible for adding methyl groups from   DNA adenosylmethionine (SAM) to cytosines. DNMT1 is the maintenance methyltransferase and DNMT3a and DNMT3b are de novo methyltransferases.  
  • ENCODE: The Encyclopedia of DNA Elements is an International Consortium of research groups which have and continue to develop a comprehensive description of functional elements in the human genome. For epigenetic engineers, this represents an immense resource of pre-existing epigenome data.  
  • enhancer, gene enhancer: any functional sequence of DNA that regulates, generally promotes, transcriptional activity of a target gene or set of target genes through distal DNA looping.    
  • epi-disease, epigenetic disease: any disease that has an epigenetic origin.
  • epigene editing, epigenetic editing: the act of altering local epigenetic features, such as  histone modification patterns, to achieve a particular structure or  regulatory response in DNA. For example, local chromatin compaction to reduce target gene transcription.  
  • epigenetic code: the entire catalog of potential epigenetic modifications that regulate DNA structure and expression.
  • epigenetic engineerging: the act of altering local epigenetic features, such as histone  modification patterns, to achieve a particular structure or regulatory  response in DNA. Can also see epigenetic editing.
  • epigenetic mechanisms: generic term used to describe any system or part of system capable of altering epigenetic features.
  • epigenetic "memory": involves the retention of an epigenetic change after initial stimulous. Can be a biomarker or alter function.
  • epigenetic modifying tools, epigenetic tool kit: the adaptation of natural enzymes capable of altering epigenetic features into custom epigenetic editing tools by connecting them with protein-DNA homing systems such as CRISPR/Cas. The use of "tool kit," implies specifically a collection of available epi-modifying enzymes that can be used for specific epigenetic modifying strategies. 
  • epigenetic RNA: RNA  that functions in regulating genome presentation by directly interacting with DNA or associated epigenetic and chromatin remodeling complexes.  
  • epigenetic therapies, epi-therapies: therapies aimed at correcting epigenetic or epigenome dysfunction.
  • epigenome: refers to the entire collection of epigenetic modifications that regulate the presentation and expression of the genome.       
  • epigenome data: genome-wide data collections of distinct epigenetic features such as DNA methylation or histone modifications.     
  • epigenome dysregulation: any alteration to typical genome-wide DNA structural and  expression.
  • epigenome enginnering, epigenomic engineering: the act of altering multiple epigenetic features to tailor genome presentation. Whereas epigenetic editing refers to local, often gene specific, epigenome editing or engineering refers to global editing strategies. These can be crude relatively non-specific genome-wide  modifiers such as demethylation by 5 azacytidine, or highly specific editing with homing systems at multiple loci simultaneously or in sequence. 
  • epimod, epimodifiers: short hand for any epigenetic modification. Any enzyme capable of carrying out an "epi-mod" can be referred generically as an "epimodifier." 
  • epi-mutation: any abnormal change to an epigenetic feature.  
  • expresssion, transcription: refers to the copying of DNA information in the form of RNA using specialized enzymes such as RNA polymerase. In the central dogma of molecular biology, this classically refers to production of "messenger" RNA, but most of the genome is expressed and many are epigenetic RNAs. see epigenetic RNA.
  • extruded, reeled, looped (DNA): refers to the processive pulling of DNA through condensin complexes to loop out DNA. 
  • fusion, gene fusion: the act of linking distinct genetic sequences together typically with recombinant DNA technology so that amino acid sequences are produces in sequence during translation.            

KEY TERMS (G-T)

  • gene: a portion of the genome that codes for a particular protein sequence. ~1% of the genome codes for proteins.        
  • gene editing: altering DNA sequences in living cells, specifically gene sequences.    
  • gene promoter: a functional genome element that is typically found at and around the 5' transcription start site for a gene. The recruitment of transcription factors to promoters is very important for regulating gene expression. 
  • genetic code: refers to the DNA to amino acid conversion code used by cells to arrange the order of amino acids linked together during protein translation. 
  • genome: the entire DNA sequence of a cell or organism.    
  • genome coordinate: represents a unique position within the genome. Typically this is an exact DNA sequence position on a particular chromosome.    
  • genome editing, genome engineering: editing DNA on global scale. Typically refers to the   targeting of any or multiple loci for DNA cutting and/or replacement   strategies.
  • genome expression: refers to the collective RNA produced by a genome as regulated by the   epigenome.   
  • gRNA design tool: a generic term used to describe a number of availalable cr or gRNA design tools   for rapidly choosing Cas9 homing RNAs. Similar in concept, most search for ~20 bp specific sequences avoiding similar sequences elsewhere for off   targeting, and requiring the protospacer adjacent motif (PAM) 
  • gRNA, crRNA: small RNAs which guide Cas protein to target sequences for digestion. For gene  editing, this in in reference to "guide" RNAs directing Cas protein   to a unique DNA coordinate.    
  • histone acetyl transferase, HAT: a specialized enzyme capable of adding acetyl groups to histone tails.      
  • histone deacetylase, HDAC: a specialized enzyme capable of removing acetyl groups from histone tails.
  • histone methylation: the act of adding a methyl group to distinct lysine and arginine amino acids   of histone tails.
  • histone mod: short hand for any modification to histones.
  • histone tail: extending out from the histone core, the n-terminal tail is rich in amino acids which can enzymatically modified. These modifications can alter local DNA-histone interactions and change gene expression.  
  • histones: basic proteins with a highly positive charge that are intimately wrapped by negatively charged DNA. An octomer of histones represent the core structure of the nucleosome.      
  • home, homing: to find a unique location among many candidates.
  • homing coordinates: any unique DNA or RNA location capable of targeting by a homing protein or   RNA.   
  • homing proteins: proteins with the innate or researcher enabled capacity to find a unique DNA   sequence among many candidates.
  • homologous recombination: an accurate DNA repair pathway that utilizes a repair template the replace missing DNA generated from a DNA double-strand break. 
  • imprinting: refers to a subset of genes or loci that are expressed in a parent of origin manner as   controlled by epigenetic mechanisms. 
  • in vitro: test tube or culture dish setting outside of a living organism.
  • in vivo: testing within a live organism.  
  • looping, DNA looping, extrusion:  refers to the processive pulling of DNA through condensin complexes to loop out DNA. 
  • massively parallel  sequencing technologies: "next generation sequencing" technologies that rely on simultaneous sequencing of millions of DNA sequences and the   reassembly of these sequences using sequence alignment algorithms and existing reference genomes. 
  • methylation, dna: the addition of methyl groups to DNA. This predominately occurs at CpG   dinucleotides using DNA methyltransferase enzymes and co-factor DNA adenosylmethionine (SAM).
  • methylation, histone: the act of adding a methyl group to distint lysine and arginine amino acids of histone tails.
  • methylome: the entire collection of methylated and unmethylated cytosines for an entire cell or   tissue.  
  • mRNA, transcribed, transcription: in the central dogma of molecular biology, "messenger" or mRNA is transcribed from genes, modified and   exported into the cytoplasm, and ultimately translated into protein.  
  • non-homologous end joining: a rapid, but inaccurate DNA double-strand break repair system that results in small insertions and deletions. Useful for generating gene knockouts using gene editing. 
  • nuclease: an enzyme capable of digesting DNA or RNA.            
  • nucleosome: an octomer of histones wrapped by 146 bp of DNA.   
  • PAM: protospacer adajcent motif. Refers to the sequence directly next to the protospacer in CRISPR/Cas based gene editing. The protospacer is the part of the cr or gRNA   sequence that complements the intended target. For Cas9 this is NGG, where N refers to any DNA letter.
  • plasmid: a small double stranded circle of DNA found in varying quantities in bacteria.  Whereas a larger plasmid constitutes most of a bacterium's genome, smaller   plasmids can be replicated and shared between bacteria. 
  • recombinant DNA technology: the act of combining any pieces of DNA together to obtain a new   function. Originally invented in the 1970's, this technology is critical for   forming new variants of custom genetic and epigenetic editing enyzmes.
  • repair template: in gene editing, refers to the delivery of a piece of DNA with replacement sequences for a particular researcher defined DNA double-strand break. This   DNA is required to have homologous sequences with the target cut site.   
  • repetitive element: refers to any one of many forms of repeating DNA sequences common to genomes. For example a class of repetitive short inerspersed nuclear elements called Alu make up nearly 11% of the entire human genome.
  • RNA polymerase: an enzyme capable of transcribing DNA into RNA. Genes are transcribed by   RNAPII. 
  • road maps, epigenetic maps: a term used to describe epigenome data sets of disease or development, where epigenetic changes can be connected with one another or genome expression over time. Useful for finding new genome and epigenome engineering   coordinates. 
  • restriction enzyme: a special class of enzymes that naturally home to and cut specific DNA sequences.
  • silencing RNA, siRNA: a class of short RNAs that complement mRNAs based on sequence. When processed and bound to a target mRNA, the mRNA is digested the RNA silencing proteins including AGO. 
  • talen, tale: transcription factor like effector + nuclease. Refers to a naturally existing class of transcription factors in Xanthomons bacteria, which based on a   repetitive sequence code, can bind to unique DNA sequences. This code can be   used by researchers to generate new sequence specific homing nucleases (TALENs) or DNA binding transcription factors (TALEs). 
  • TET: ten-eleven translocation enzyme. An initiating member of the DNA demethylation pathway, TET proteins oxidize 5-methylcytosine into 5-hydroxymethylcytosine and other derivatives.                      

Key Terms (T-Z)

  •  tracrRNA: contains homology to a short palindromic repeat and helps recuit Cas proteins during RNA processing. For gene editing purposes, this RNA base pairs with crRNA or gRNAs to form a functional homing system, where the tracrRNA constitutes a Cas protein handle and the gRNA binds that actual target DNA. 
  • transcribed, transcription, mRNA: in the central dogma of molecular biology,   "messenger" or mRNA is transcribed from genes, modified and   exported into the cytoplasm, and ultimately translated into protein. 
  • transcription factor: any protein factor (often aided by a homing RNA) that can bind and regulates   gene or genome expression.
  • transgenerational epigenetic inheritence: when epigenetic modifications are inherited through the germ-line (e.g. in sperm cells) and passed on generation-to-generation.    
  • X-chromosome inactivation: refers to the silencing of 1 of the 2 X chromosomes present in female mammals. This epigenetic program relies heavily on long-noncoding RNA and DNA methylation. 
  • zinc finger nuclease, zfn: zinc finger refers specifically a naturally occurring protein domain of   many transcription factors, which is stabilized by a zinc ion. These domains   bind to unique DNA sequences and can be designed for specific binding by researchers. The use of DNA cutting activity specifically involves the incorporation of nuclease function.