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A regulator gene, regulator, or regulatory gene is a
gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ...
involved in controlling the expression of one or more other genes.
Regulatory sequence A regulatory sequence is a segment of a nucleic acid molecule which is capable of increasing or decreasing the expression of specific genes within an organism. Regulation of gene expression is an essential feature of all living organisms and vi ...
s, which encode regulatory genes, are often at the five prime end (5') to the start site of transcription of the gene they regulate. In addition, these sequences can also be found at the three prime end (3') to the
transcription start site Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules calle ...
. In both cases, whether the regulatory sequence occurs before (5') or after (3') the gene it regulates, the sequence is often many kilobases away from the transcription start site. A regulator gene may encode a protein, or it may work at the level of
RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
, as in the case of genes encoding
microRNA MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRN ...
s. An example of a regulator gene is a gene that codes for a
repressor In molecular genetics, a repressor is a DNA- or RNA-binding protein that inhibits the expression of one or more genes by binding to the operator or associated silencers. A DNA-binding repressor blocks the attachment of RNA polymerase to the ...
protein that inhibits the activity of an operator (a gene which binds repressor proteins thus inhibiting the
translation Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transl ...
of RNA to protein via
RNA polymerase In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that synthesizes RNA from a DNA template. Using the enzyme helicase, RNAP locally opens the ...
). In
prokaryotes A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Con ...
, regulator genes often code for repressor proteins. Repressor proteins bind to operators or promoters, preventing
RNA polymerase In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that synthesizes RNA from a DNA template. Using the enzyme helicase, RNAP locally opens the ...
from transcribing RNA. They are usually constantly expressed so the cell always has a supply of repressor molecules on hand.
Inducer In molecular biology, an inducer is a molecule that regulates gene expression. An inducer functions in two ways; namely: *By disabling repressors. The gene is expressed because an inducer binds to the repressor. The binding of the inducer to t ...
s cause repressor proteins to change shape or otherwise become unable to bind DNA, allowing RNA polymerase to continue transcription. Regulator genes can be located within an
operon In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo spli ...
, adjacent to it, or far away from it. Other regulatory genes code for activator proteins. An activator binds to a site on the DNA molecule and causes an increase in transcription of a nearby gene. In prokaryotes, a well-known activator protein is the
catabolite activator protein Catabolite activator protein (CAP; also known as cAMP receptor protein, CRP) is a trans-acting transcriptional activator that exists as a homodimer in solution. Each subunit of CAP is composed of a ligand-binding domain at the N-terminus (CAPN, ...
(CAP), involved in positive control of the
lac operon The ''lactose'' operon (''lac'' operon) is an operon required for the transport and metabolism of lactose in ''E. coli'' and many other enteric bacteria. Although glucose is the preferred carbon source for most bacteria, the ''lac'' operon allo ...
. In the
regulation of gene expression Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are wid ...
, studied in
evolutionary developmental biology Evolutionary developmental biology (informally, evo-devo) is a field of biological research that compares the developmental processes of different organisms to infer how developmental processes evolved. The field grew from 19th-century begin ...
(evo-devo), both activators and repressors play important roles. Regulatory genes can also be described as positive or negative regulators, based on the environmental conditions that surround the cell. Positive regulators are regulatory elements that permit RNA polymerase binding to the promoter region, thus allowing transcription to occur. In terms of the lac operon, the positive regulator would be the CRP-cAMP complex that must be bound close to the site of the start of transcription of the lac genes. The binding of this positive regulator allows RNA polymerase to bind successfully to the promoter of the lac gene sequence which advances the transcription of lac genes; lac Z, lac Y, and lac A. Negative regulators are regulatory elements which obstruct the binding of RNA polymerase to the promoter region, thus repressing transcription. In terms of the lac operon, the negative regulator would be the lac repressor which binds to the promoter in the same site that RNA polymerase normally binds. The binding of the lac repressor to RNA polymerase's binding site inhibits the transcription of the lac genes. Only when a corepressor is bound to the lac repressor will the binding site be free for RNA polymerase to carry out transcription of the lac genes.


Gene regulatory elements

Promoters reside at the beginning of the gene and serve as the site where the
transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...
machinery assembles and transcription of the gene begins.
Enhancers In genetics, an enhancer is a short (50–1500 bp) region of DNA that can be bound by proteins ( activators) to increase the likelihood that transcription of a particular gene will occur. These proteins are usually referred to as transcriptio ...
turn on the promoters at specific locations, times, and levels and can be simply defined as the “promoters of the promoter.” Silencers are thought to turn off gene expression at specific time points and locations. Insulators, also called boundary elements, are DNA sequences that create cis-regulatory boundaries that prevent the regulatory elements of one gene from affecting neighboring genes. The general dogma is that these regulatory elements get activated by the binding of
transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
s, proteins that bind to specific DNA sequences, and control
mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during t ...
transcription. There could be several transcription factors that need to bind to one regulatory element in order to activate it. In addition, several other proteins, called transcription cofactors, bind to the transcription factors themselves to control transcription.


Negative regulators

Negative regulators act to prevent transcription or translation. Examples such as cFLIP suppress
cell death Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, as in programmed cell death, or may result from factors such as di ...
mechanisms leading to pathological disorders like
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...
, and thus play a crucial role in
drug resistance Drug resistance is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in treating a disease or condition. The term is used in the context of resistance that pathogens or cancers have "acquired", that is ...
. Circumvention of such actors is a challenge in
cancer therapy Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal ble ...
. Negative regulators of cell death in cancer include cFLIP, Bcl2 family,
Survivin Survivin, also called baculoviral inhibitor of apoptosis repeat-containing 5 or BIRC5, is a protein that, in humans, is encoded by the ''BIRC5'' gene. Survivin is a member of the inhibitor of apoptosis (IAP) family. The survivin protein functions ...
, HSP, IAP,
NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellula ...
,
Akt Protein kinase B (PKB), also known as Akt, is the collective name of a set of three serine/threonine-specific protein kinases that play key roles in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transc ...
,
mTOR The mammalian target of rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the ''MTOR'' gene. ...
, and
FADD FAS-associated death domain protein, also called MORT1, is encoded by the ''FADD'' gene on the 11q13.3 region of chromosome 11 in humans. FADD is an adaptor protein that bridges members of the tumor necrosis factor receptor superfamily, such ...
.


Detection

There are several different techniques to detect regulatory genes, but of the many there are a certain few that are used more frequently than others. One of these select few is called ChIP-chip.
ChIP-chip ChIP-on-chip (also known as ChIP-chip) is a technology that combines chromatin immunoprecipitation ('ChIP') with DNA microarray (''"chip"''). Like regular ChIP, ChIP-on-chip is used to investigate interactions between proteins and DNA ''in vivo ...
is an in vivo technique used to determine
genomic Genomics is an interdisciplinary field of biology focusing on the structure, function, evolution, mapping, and editing of genomes. A genome is an organism's complete set of DNA, including all of its genes as well as its hierarchical, three-dim ...
binding sites for transcription factors in two component system response regulators.
In vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...
microarray A microarray is a multiplex lab-on-a-chip. Its purpose is to simultaneously detect the expression of thousands of genes from a sample (e.g. from a tissue). It is a two-dimensional array on a solid substrate—usually a glass slide or silicon ...
based assay (DAP-chip) can be used to determine gene targets and functions of two component
signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellular ...
systems. This assay takes advantage of the fact that response regulators can be phosphorylated and thus activated in vitro using small molecule donors like acetyl phosphate.


Phylogenetic footprinting

Phylogenetic footprinting is a technique that utilizes
multiple sequence alignment Multiple sequence alignment (MSA) may refer to the process or the result of sequence alignment of three or more biological sequences, generally protein, DNA, or RNA. In many cases, the input set of query sequences are assumed to have an evolut ...
s to determine locations of
conserved sequence In evolutionary biology, conserved sequences are identical or similar sequences in nucleic acids ( DNA and RNA) or proteins across species ( orthologous sequences), or within a genome ( paralogous sequences), or between donor and receptor taxa ( ...
s such as regulatory elements. Along with multiple sequence alignments, phylogenetic footprinting also requires statistical rates of conserved and non-conserved sequences. Using the information provided by multiple sequence alignments and statistical rates, one can identify the best conserved motifs in the
orthologous Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spec ...
regions of interest.


References


External links


Plant Transcription Factor Database
* {{MeshName, Regulator+Gene * http://www.news-medical.net/life-sciences/Gene-Expression-Techniques.aspx * http://www.britannica.com/science/regulator-gene * https://www.boundless.com/biology/textbooks/boundless-biology-textbook/gene-expression-16/regulation-of-gene-expression-111/prokaryotic-versus-eukaryotic-gene-expression-453-11678/ Gene expression