Transcriptional regulationIn 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.
Histone deacetylaseHistone deacetylases (, HDAC) are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on both histone and non-histone proteins. HDACs allow histones to wrap the DNA more tightly. This is important because DNA is wrapped around histones, and DNA expression is regulated by acetylation and de-acetylation. HDAC's action is opposite to that of histone acetyltransferase. HDAC proteins are now also called lysine deacetylases (KDAC), to describe their function rather than their target, which also includes non-histone proteins.
Transcription (biology)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 called non-coding RNAs (ncRNAs). mRNA comprises only 1–3% of total RNA samples. Less than 2% of the human genome can be transcribed into mRNA (Human genome#Coding vs. noncoding DNA), while at least 80% of mammalian genomic DNA can be actively transcribed (in one or more types of cells), with the majority of this 80% considered to be ncRNA.
SirtuinSirtuins are a family of signaling proteins involved in metabolic regulation. They are ancient in animal evolution and appear to possess a highly conserved structure throughout all kingdoms of life. Chemically, sirtuins are a class of proteins that possess either mono-ADP-ribosyltransferase or deacylase activity, including deacetylase, desuccinylase, demalonylase, demyristoylase and depalmitoylase activity. The name Sir2 comes from the yeast gene 'silent mating-type information regulation 2', the gene responsible for cellular regulation in yeast.
Regulation of gene expressionRegulation 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.
HistoneIn biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. 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.
Cis-regulatory elementCis-regulatory elements (CREs) or Cis''-regulatory modules (CRMs) are regions of non-coding DNA which regulate the transcription of neighboring genes. CREs are vital components of genetic regulatory networks, which in turn control morphogenesis, the development of anatomy, and other aspects of embryonic development, studied in evolutionary developmental biology. CREs are found in the vicinity of the genes that they regulate. CREs typically regulate gene transcription by binding to transcription factors.
Regulatory sequenceA 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 viruses. In DNA, regulation of gene expression normally happens at the level of RNA biosynthesis (transcription). It is accomplished through the sequence-specific binding of proteins (transcription factors) that activate or inhibit transcription.
Transcription factorIn 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 function of TFs is to regulate—turn on and off—genes in order to make sure that they are expressed in the desired cells at the right time and in the right amount throughout the life of the cell and the organism.
Histone acetyltransferaseHistone acetyltransferases (HATs) are enzymes that acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl-CoA to form ε-N-acetyllysine. DNA is wrapped around histones, and, by transferring an acetyl group to the histones, genes can be turned on and off. In general, histone acetylation increases gene expression. In general, histone acetylation is linked to transcriptional activation and associated with euchromatin.
Histone deacetylase inhibitorHistone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are chemical compounds that inhibit histone deacetylases. HDIs have a long history of use in psychiatry and neurology as mood stabilizers and anti-epileptics. More recently they are being investigated as possible treatments for cancers, parasitic and inflammatory diseases. To carry out gene expression, a cell must control the coiling and uncoiling of DNA around histones.
Histone acetylation and deacetylationHistone acetylation and deacetylation are the processes by which the lysine residues within the N-terminal tail protruding from the histone core of the nucleosome are acetylated and deacetylated as part of gene regulation. Histone acetylation and deacetylation are essential parts of gene regulation. These reactions are typically catalysed by enzymes with "histone acetyltransferase" (HAT) or "histone deacetylase" (HDAC) activity. Acetylation is the process where an acetyl functional group is transferred from one molecule (in this case, acetyl coenzyme A) to another.
Chromatin remodelingChromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression. Such remodeling is principally carried out by 1) covalent histone modifications by specific enzymes, e.g., histone acetyltransferases (HATs), deacetylases, methyltransferases, and kinases, and 2) ATP-dependent chromatin remodeling complexes which either move, eject or restructure nucleosomes.
Activator (genetics)A transcriptional activator is a protein (transcription factor) that increases transcription of a gene or set of genes. Activators are considered to have positive control over gene expression, as they function to promote gene transcription and, in some cases, are required for the transcription of genes to occur. Most activators are DNA-binding proteins that bind to enhancers or promoter-proximal elements. The DNA site bound by the activator is referred to as an "activator-binding site".
Gene expressionGene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, and ultimately affect a phenotype. These products are often proteins, but in non-protein-coding genes such as transfer RNA (tRNA) and small nuclear RNA (snRNA), the product is a functional non-coding RNA.
Regulator geneA regulator gene, regulator, or regulatory gene is a gene involved in controlling the expression of one or more other genes. Regulatory sequences, 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. 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.
PhysiologyPhysiology (ˌfɪziˈɒlədʒi; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical and physical functions in a living system. According to the classes of organisms, the field can be divided into medical physiology, animal physiology, plant physiology, cell physiology, and comparative physiology.
Oxidative stressOxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Oxidative stress from oxidative metabolism causes base damage, as well as strand breaks in DNA.
