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Chromatin Variant
A chromatin variant corresponds to a section of the genome that differs in chromatin states across cell types/states within an individual (intra-individual) or between individuals for a given cell type/state (inter-individual). Chromatin variants distinguish DNA sequences that differ in their function in one cell type/state versus another. Chromatin variants are found across the genome, inclusive of repetitive and non-repetitive DNA sequence. Chromatin variants range in sizes. The smallest chromatin variants cover a few hundred DNA base pairs, such as seen at promoters, enhancers or insulators. The largest chromatin variants capture a few thousand DNA base pairs, such as seen at Large Organized Chromatin Lysine domains (LOCKs) and Clusters Of Cis-Regulatory Elements (COREs), such as super-enhancer In genetics, a super-enhancer is a region of the mammalian genome comprising multiple enhancers that is collectively bound by an array of transcription factor proteins to drive transcript ...
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Genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as regulatory sequences (see non-coding DNA), and often a substantial fraction of 'junk' DNA with no evident function. Almost all eukaryotes have mitochondria and a small mitochondrial genome. Algae and plants also contain chloroplasts with a chloroplast genome. The study of the genome is called genomics. The genomes of many organisms have been sequenced and various regions have been annotated. The International Human Genome Project reported the sequence of the genome for ''Homo sapiens'' in 200The Human Genome Project although the initial "finished" sequence was missing 8% of the genome consisting mostly of repetitive sequences. With advancements in technology that could handle sequenci ...
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Chromatin
Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in reinforcing the DNA during cell division, preventing DNA damage, and regulating gene expression and DNA replication. During mitosis and meiosis, chromatin facilitates proper segregation of the chromosomes in anaphase; the characteristic shapes of chromosomes visible during this stage are the result of DNA being coiled into highly condensed chromatin. The primary protein components of chromatin are histones. An octamer of two sets of four histone cores (Histone H2A, Histone H2B, Histone H3, and Histone H4) bind to DNA and function as "anchors" around which the strands are wound.Maeshima, K., Ide, S., & Babokhov, M. (2019). Dynamic chromatin organization without the 30-nm fiber. ''Current opinion in cell biology, 58,'' 95–104. https://doi.o ...
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Cell Types
A cell type is a classification used to identify cells that share morphological or phenotypical features. A multicellular organism may contain cells of a number of widely differing and specialized cell types, such as muscle cells and skin cells, that differ both in appearance and function yet have identical genomic sequences. Cells may have the same genotype, but belong to different cell types due to the differential regulation of the genes they contain. Classification of a specific cell type is often done through the use of microscopy (such as those from the cluster of differentiation family that are commonly used for this purpose in immunology). Recent developments in single cell RNA sequencing facilitated classification of cell types based on shared gene expression patterns. This has led to the discovery of many new cell types in e.g. mouse cortex, hippocampus, dorsal root ganglion and spinal cord. Animals have evolved a greater diversity of cell types in a multicellular bod ...
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Individual
An individual is that which exists as a distinct entity. Individuality (or self-hood) is the state or quality of being an individual; particularly (in the case of humans) of being a person unique from other people and possessing one's own Maslow's hierarchy of needs, needs or goals, rights and moral responsibility, responsibilities. The concept of an individual features in diverse fields, including biology, law, and philosophy. Etymology From the 15th century and earlier (and also today within the fields of statistics and metaphysics) ''individual'' meant "divisible, indivisible", typically describing any numerically singular thing, but sometimes meaning "a person". From the 17th century on, ''individual'' has indicated separateness, as in individualism. Law Although individuality and individualism are commonly considered to mature with age/time and experience/wealth, a sanity, sane adult human, human being is usually considered by the State (polity), state as an "individu ...
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Promoter (genetics)
In genetics, a promoter is a sequence of DNA to which proteins bind to initiate transcription of a single RNA transcript from the DNA downstream of the promoter. The RNA transcript may encode a protein (mRNA), or can have a function in and of itself, such as tRNA or rRNA. Promoters are located near the transcription start sites of genes, upstream on the DNA (towards the 5' region of the sense strand). Promoters can be about 100–1000 base pairs long, the sequence of which is highly dependent on the gene and product of transcription, type or class of RNA polymerase recruited to the site, and species of organism. Promoters control gene expression in bacteria and eukaryotes. RNA polymerase must attach to DNA near a gene for transcription to occur. Promoter DNA sequences provide an enzyme binding site. The -10 sequence is TATAAT. -35 sequences are conserved on average, but not in most promoters. Artificial promoters with conserved -10 and -35 elements transcribe more slowly. All D ...
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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 transcription factors. Enhancers are ''cis''-acting. They can be located up to 1 Mbp (1,000,000 bp) away from the gene, upstream or downstream from the start site. There are hundreds of thousands of enhancers in the human genome. They are found in both prokaryotes and eukaryotes. The first discovery of a eukaryotic enhancer was in the immunoglobulin heavy chain gene in 1983. This enhancer, located in the large intron, provided an explanation for the transcriptional activation of rearranged Vh gene promoters while unrearranged Vh promoters remained inactive. Locations In eukaryotic cells the structure of the chromatin complex of DNA is folded in a way that functionally mimics the supercoiled state characteristic of prokaryotic DNA, so although the enh ...
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Insulator (genetics)
An insulator is a type of cis-regulatory element known as a long-range regulatory element. Found in multicellular eukaryotes and working over distances from the promoter element of the target gene, an insulator is typically 300 bp to 2000 bp in length. Insulators contain clustered binding sites for sequence specific DNA-binding proteins and mediate intra- and inter-chromosomal interactions. Insulators function either as an enhancer-blocker or a barrier, or both. The mechanisms by which an insulator performs these two functions include loop formation and nucleosome modifications. There are many examples of insulators, including the CTCF insulator, the ''gypsy'' insulator, and the β-globin locus. The CTCF insulator is especially important in vertebrates, while the ''gypsy'' insulator is implicated in ''Drosophila.'' The β-globin locus was first studied in chicken and then in humans for its insulator activity, both of which utilize CTCF. The genetic implications of insulators ...
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Super-enhancer
In genetics, a super-enhancer is a region of the mammalian genome comprising multiple enhancers that is collectively bound by an array of transcription factor proteins to drive transcription of genes involved in cell identity. Because super-enhancers are frequently identified near genes important for controlling and defining cell identity, they may thus be used to quickly identify key nodes regulating cell identity. Enhancers have several quantifiable traits that have a range of values, and these traits are generally elevated at super-enhancers. Super-enhancers are bound by higher levels of transcription-regulating proteins and are associated with genes that are more highly expressed. Expression of genes associated with super-enhancers is particularly sensitive to perturbations, which may facilitate cell state transitions or explain sensitivity of super-enhancer—associated genes to small molecules that target transcription. History The regulation of transcription by enhancers h ...
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Gene Expression
Gene 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, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. 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. Gene expression is summarized in the central dogma of molecular biology first formulated by Francis Crick in 1958, further developed in his 1970 article, and expanded by the subsequent discoveries of reverse transcription and RNA replication. The process of gene expression is used by all known life—eukaryotes (including multicellular organisms), prokaryotes (bacteria and archaea), and utilized by viruses—to generate the macromolecular machinery for life. In genetics, gene expression is the most fundamental level at which the genotype gives rise to the phenotype, '' ...
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