Drug Action Glossary

Activator

a protein that stimulates the expression of a gene, typically by acting at a promoter to stimulate RNA polymerase. In eukaryotes, the sequence to which it binds the promoter is caller response element.

Allele

one of several forms of gene occupying a given locus of the chromosome.

Basal Factor

a transcription factor required by RNA polymerase II to form the initiation complex at all promoters. Factors are identified as TFIIX, where X is a number

Basal transcription apparatus

the complex of transcription factors that assembles at the promoter

before RNA polymerase is bound.

cDNA

single-stranded DNA complementary to an RNA, synthesized from it by reverse transcription in vitro.

Cell Cycle

set of stages through which cell progresses from one division to the next.

Chaperones

class of proteins that bind to incompletely folded or assembled proteins in order to assist their folding or prevent them from aggregating.

Chromatin

the state of nuclear DNA associated with proteins during interphase (between mitoses) in eukaryotic cells.

chromatin remodeling

energy-dependent displacement or reorganization of nucleosomes that occurs in conjunction with activation of gene transcription.

Chromosome

a discrete unit of the genome carrying many genes, consists of a very long molecule of duplex DNA and approximately equal mass of proteins. It is visible as a morphological entity only during cell division

co-activator

factor required for transcription that do not bind DNA but required for DNA-binding activator to interact with the basal transcription factors

codon

a triplet of nucleotides represents an amino acid or a termination signal.

Core DNA

the 146 bp of DNA contained in a core particle.

Core histone

one of the H2A, H2B, H3 and H4 histones found in the core particle derived from the nucleosome, excludes H1.

Core particle

a digestion product of the nucleosome that retains the histone octamer and has 146 bp of DNA, its structure appears similar to nucleosome.

Core promoter

The region immediately surrounding the start point. It is necessary to initiate transcription, but only in a low level.

Co-repressor

small molecule that triggers repression of transcription by binding to a regulator protein.

Enhancers

cis-acting DNA regulatory elements that increase the transcriptional output of target genes

Epigenetic changes

influence the phenotype without altering the genotype. They consist of changes in the properties of a cell that are inherited but do not represent a change in genetic information.

Epitope

is the portion of an antigen that is recognized by the antigen receptor on lymphocytes.

Euchromatin

comprises all the genome in the interphase nucleus except for the heterochromatin. The euchromatin is less tightly coiled than heterochromatin and contains the active or potentially active genes

Exon

any segment of an interrupted gene that is represented in the mature RNA product.

Genetic code

the correspondence between triplets in DNA or RNA and amino acids in protein.

Genome instability

a state in which there is a large increase.100-fold in the frequency of changes in the genome as seen by chromosomal rearrangements or other events that affect the genetic content. This is a key occurrence in the generation of cancer cells.

Genome

the complete set of sequences in the genetic material of an organism. It includes the sequence of each chromosome plus any DNA organelles.

Haplotype

a particular combination of alleles in a define region of a chromosome.

Histones

conserved DNA-binding proteins that form the basic subunit of chromatin eukaryotes. Histones H2A, H2B, H3, H4 form an octameric core around which DNA coils to form a nucleosome. Histone H1 is external to nucleosome.

Histone acetyle-transferase (HAT)

enzyme modifies histones by addition of acetyl groups, some

transcriptional activators have HAT activity.

Histone de-acetyl-transferase (HDAC)

enzyme removes acetyl groups from histones, they are

associated with transcriptional repressors.

Intron

segment of DNA that is transcribed but removed from within the transcript by splicing together sequences (exons) on either side of it

Locus

the position on a chromosome at which the gene for a particular trait resides, a locus might be occupied by any one of the alleles of the genes.

Nucleosome

the basic structural unit of chromatin consisting of 200 bp of DNA and an octamer of histone proteins.

promoter

critical element that can work in concert with other regulatory regions (enhancers, silencers, insulators) to direct the level of transcription of a given gene, the starting point of RNA synthesis

Silencing

describes the repression of gene expression in a localized region, usually as the result of a structural change in chromatin.

Single Nucleotide polymorphism (SNP)

a variation in sequence between individuals caused by a change in a single nucleotide. This is responsible for most of the genetic variation between individuals.

Synteny

a relationship between chromosomal regions of different species where homologous genes occur in the same order.

TF_IID

the transcription factor that binds to TATA sequence upstream of the start point of promoters for

RNA polymerase II. It consists of TBP (TATA binding protein) and the TAF subunits that bind to TBP.

Transcription Factor

protein required for RNA polymerase to initiate transcription at specific

promoters but is not itself part of the enzyme.

Transcription Unit

the distance between sites of initiation and termination by RNA polymerase, may include more than one gene.

Transgene

a gene that is introduced into a cell or animal from an external source.

Telomeres

repetitive DNA sequences at the ends of linear chromosomes that protect them from deterioration and fusion

Centromeres

constricted chromosomal regions essential for the proper segregation of chromosomes during cell division

Gene

a sequence of DNA that encodes a functional product, typically a protein or RNA

Non-coding DNA

Most of the DNA does not code for proteins. This includes non-coding RNA genes, regulatory sequences, and repetitive DNA.

Repetitive DNA

The genome contains various repeated sequences, such as Short and Long Interspersed Elements (SINEs and LINEs), which can contribute to genomic complexity and evolution.

Multigene Families

some genes, such ribosomal RNA or histones, are present in multiple copies or families

Chromatin accessibility

Genes in loosely packed euchromatin are more accessible for transcription than those in tightly packed heterochromatin.

Transcriptional Control

Regulatory proteins, transcription factors bind to specific DNA sequences like promoters and enhancers to control the initiation of transcription by RNA polymerase.

Post- Transcriptional control

Regulation that occurs after transcription

Alternative splicing

pre-mRNA can be spliced in different ways to produce multiple protein isoforms, greatly increasing proteomic diversity.

RNA stability

The lifespan of mRNA can be regulated, affecting the production of protein.

Translational and post-translational control

Gene expression is regulated during the translation of mRNA into protein or through modifications to the finished protein itself

Signaling cascades

External or internal signals trigger a cascade of events that modify TFs. (phosphorylation or a ligand can bind to a TF to trigger a conformational change)

Protein-protein interactions

TFs can interact with other proteins, including other TFs, co-activators, or co-repressors, to form complexes that activate or repress transcription

Post-translational modifications (PTMs)

Covalent modifications like phosphorylation, acetylation, and glycosylation can alter a TF's activity, stability, or nuclear localization

Histone Modification

Enzymes can modify histone proteins, altering how tightly the DNA is wound

Chromatin Remodeling Complexes

ATP-dependent protein complexes can physically move or restructure nucleosomes (DNA-histone units) to expose or hide DNA sequences

DNA Methylation

Methyl groups can be added directly to DNA, typically at CpG sites and leads to transcriptional repression by attracting proteins that compact chromatin

microRNAs (miRNAs)

small RNA molecules that can reduce gene expression by binding to mRNA, leading to mRNA degradation or inhibition of translation

Allele frequency

Number of copies of a particular allele, in the population

Penetrance

The proportion of people with a particular genetic disorder exhibiting s/s of a genetic disorder

Genetics

the study of single gene and its effects

Genomics

The study of all genes in the genome, including their interactions with environmental factors

Pharmacogenomics

The study of how genes affect a person’s response to drugs

precision medicine

An emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person

Gene editing

the ability to make highly specific changes in the DNA sequences of a living organism, essentially customizing its genetic makeup

antisense oligonucleotides

a gene silencing tool that is a synthetic pieces of DNA or RNA that target the messenger RNA to prevent a disease-causing protein from being made

RNA interference (RNAi)

a gene silencing tool that uses small RNAs to “silence“ a targeted gene by neutralizing the gene’s mRNA

Messanger RNAs (mRNA)

introduces genetic code into cells