Gene regulation in the context of "Post-translational modification"

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⭐ Core Definition: Gene regulation

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 widely observed in biology, for example to trigger developmental pathways, respond to environmental stimuli, or adapt to new food sources. Virtually any step of gene expression can be modulated, from transcriptional initiation, to RNA processing, and to the post-translational modification of a protein. Often, one gene regulator controls another, and so on, in a gene regulatory network.

Gene regulation is essential for viruses, prokaryotes and eukaryotes as it increases the versatility and adaptability of an organism by allowing the cell to express protein when needed. Although as early as 1951, Barbara McClintock showed interaction between two genetic loci, Activator (Ac) and Dissociator (Ds), in the color formation of maize seeds, the first discovery of a gene regulation system is widely considered to be the identification in 1961 of the lac operon, discovered by François Jacob and Jacques Monod, in which some enzymes involved in lactose metabolism are expressed by E. coli only in the presence of lactose and absence of glucose.

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Gene regulation in the context of Regulation

Regulation is the management of complex systems according to a set of rules and trends. In systems theory, these types of rules exist in various fields of biology and society, but the term has slightly different meanings according to context. For example:

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Gene regulation in the context of Regeneration (biology)

Regeneration in biology is the process of renewal, restoration, and tissue growth that makes genomes, cells, organisms, and ecosystems resilient to natural fluctuations or events that cause disturbance or damage. Every species is capable of regeneration, from bacteria to humans. Regeneration can either be complete where the new tissue is the same as the lost tissue, or incomplete after which the necrotic tissue becomes fibrotic.

At its most elementary level, regeneration is mediated by the molecular processes of gene regulation and involves the cellular processes of cell proliferation, morphogenesis and cell differentiation. Regeneration in biology, however, mainly refers to the morphogenic processes that characterize the phenotypic plasticity of traits allowing multi-cellular organisms to repair and maintain the integrity of their physiological and morphological states. Above the genetic level, regeneration is fundamentally regulated by asexual cellular processes. Regeneration is different from reproduction. For example, hydra perform regeneration but reproduce by the method of budding.

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Gene regulation in the context of Histone

In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei and in most Archaeal phyla. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wrapped into 30-nanometer fibers that form tightly packed chromatin. Histones prevent DNA from becoming tangled and protect it from DNA damage. In addition, histones play important roles in gene regulation and DNA replication. Without histones, unwound DNA in chromosomes would be very long. For example, each human cell has about 1.8 meters of DNA if completely stretched out; however, when wound about histones, this length is reduced to about 9 micrometers (0.009 mm) of 30 nm diameter chromatin fibers.

There are five families of histones, which are designated H1/H5 (linker histones), H2, H3, and H4 (core histones). The nucleosome core is formed of two H2A-H2B dimers and a H3-H4 tetramer. The tight wrapping of DNA around histones, is to a large degree, a result of electrostatic attraction between the positively charged histones and negatively charged phosphate backbone of DNA.

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Gene regulation in the context of Transcriptional regulation

In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA (transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from altering the number of copies of RNA that are transcribed, to the temporal control of when the gene is transcribed. This control allows the cell or organism to respond to a variety of intra- and extracellular signals and thus mount a response. Some examples of this include producing the mRNA that encode enzymes to adapt to a change in a food source, producing the gene products involved in cell cycle specific activities, and producing the gene products responsible for cellular differentiation in multicellular eukaryotes, as studied in evolutionary developmental biology.

The regulation of transcription is a vital process in all living organisms. It is orchestrated by transcription factors and other proteins working in concert to finely tune the amount of RNA being produced through a variety of mechanisms. Bacteria and eukaryotes have very different strategies of accomplishing control over transcription, but some important features remain conserved between the two. Most importantly is the idea of combinatorial control, which is that any given gene is likely controlled by a specific combination of factors to control transcription. In a hypothetical example, the factors A and B might regulate a distinct set of genes from the combination of factors A and C. This combinatorial nature extends to complexes of far more than two proteins, and allows a very small subset (less than 10%) of the genome to control the transcriptional program of the entire cell.

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Gene regulation in the context of 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 enteric bacteria, the lac operon allows for the effective digestion of lactose when glucose is not available through the activity of β-galactosidase. Gene regulation of the lac operon was the first genetic regulatory mechanism to be understood clearly, so it has become a foremost example of prokaryotic gene regulation. It is often discussed in introductory molecular and cellular biology classes for this reason. This lactose metabolism system was used by François Jacob and Jacques Monod to determine how a biological cell knows which enzyme to synthesize. Their work on the lac operon won them the Nobel Prize in Physiology in 1965.

Most bacterial cells including E. coli lack introns in their genome. They also lack a nuclear membrane. Hence the gene regulation by lac operon occurs at the transcriptional level, by controlling transcription of DNA.

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Gene regulation in the context of DNA condensation

DNA condensation refers to the process of compacting DNA molecules in vitro or in vivo. Mechanistic details of DNA packing are essential for its functioning in the process of gene regulation in living systems. Condensed DNA often has surprising properties, which one would not predict from classical concepts of dilute solutions. Therefore, DNA condensation in vitro serves as a model system for many processes of physics, biochemistry and biology. In addition, DNA condensation has many potential applications in medicine and biotechnology.

DNA diameter is about 2 nm, while the length of a stretched single molecule may be up to several dozens of centimetres depending on the organism. Many features of the DNA double helix contribute to its large stiffness, including the mechanical properties of the sugar-phosphate backbone, electrostatic repulsion between phosphates (DNA bears on average one elementary negative charge per each 0.17 nm of the double helix), stacking interactions between the bases of each individual strand, and strand-strand interactions. DNA is one of the stiffest natural polymers, yet it is also one of the longest molecules. The persistence length of double-stranded DNA (dsDNA) is a measure of its stiffness or flexibility, which depends on the DNA sequence and the surrounding environment, including factors like salt concentration, pH, and temperature. Under physiological conditions (e.g., near-neutral pH and physiological salt concentrations), the persistence length of dsDNA is generally around 50 nm, which corresponds to approximately 150 base pairs. This means that at large distances DNA can be considered as a flexible rope, and on a short scale as a stiff rod. Like a garden hose, unpacked DNA would randomly occupy a much larger volume than when it is orderly packed. Mathematically, for a non-interacting flexible chain randomly diffusing in 3D, the end-to-end distance would scale as a square root of the polymer length. For real polymers such as DNA, this gives only a very rough estimate; what is important, is that the space available for the DNA in vivo is much smaller than the space that it would occupy in the case of a free diffusion in the solution. To cope with volume constraints, DNA can pack itself in the appropriate solution conditions with the help of ions and other molecules. Usually, DNA condensation is defined as "the collapse of extended DNA chains into compact, orderly particles containing only one or a few molecules". This definition applies to many situations in vitro and is also close to the definition of DNA condensation in bacteria as "adoption of relatively concentrated, compact state occupying a fraction of the volume available". In eukaryotes, the DNA size and the number of other participating players are much larger, and a DNA molecule forms millions of ordered nucleoprotein particles, the nucleosomes, which is just the first of many levels of DNA packing.

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