Wnt Response Element
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Wnt Response Element
The TCF/LEF family (T cell factor/lymphoid enhancer factor family) is a group of genes that encode transcription factors which bind to DNA through a SOX-like high mobility group domain. They are involved in the Wnt signaling pathway, particularly during embryonic and stem-cell development, but also had been found to play a role in cancer and diabetes. TCF/LEF factors recruit the coactivator beta-catenin to enhancer elements of genes they target. They can also recruit members of the Groucho family of corepressors. History The discovery of the TCF/LEF genes as nuclear Wnt pathway components in the 90s was a pivotal breakthrough for the Wnt signalling research field, plugging an important knowledge gap and enabling subsequent understanding of transcriptional regulation of Wnt target genes, particularly in embryonic development and cancer. Before this discovery it was only known that upstream Wnt signalling mechanisms regulated the cytoplasmic abundance of the beta-catenin protei ...
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Transcriptional Activator
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". The part of the activator that makes protein–protein interactions with the general transcription machinery is referred to as an "activating region" or "activation domain". Most activators function by binding sequence-specifically to a regulatory DNA site located near a promoter and making protein–protein interactions with the general transcription machinery (RNA polymerase and general transcription factors), thereby facilitating the binding of the general transcription machinery to the prom ...
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Type 2 Diabetes
Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, and unexplained weight loss. Symptoms may also include increased hunger, feeling tired, and sores that do not heal. Often symptoms come on slowly. Long-term complications from high blood sugar include heart disease, strokes, diabetic retinopathy which can result in blindness, kidney failure, and poor blood flow in the limbs which may lead to amputations. The sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon. Type 2 diabetes primarily occurs as a result of obesity and lack of exercise. Some people are genetically more at risk than others. Type 2 diabetes makes up about 90% of cases of diabetes, with the other 10% due primarily to type 1 diabetes and gestational diabetes. In type 1 diabete ...
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Hair Follicle Cycle
The hair follicle is an organ found in mammalian skin. It resides in the dermal layer of the skin and is made up of 20 different cell types, each with distinct functions. The hair follicle regulates hair growth via a complex interaction between hormones, neuropeptides, and immune cells. This complex interaction induces the hair follicle to produce different types of hair as seen on different parts of the body. For example, terminal hairs grow on the scalp and lanugo hairs are seen covering the bodies of fetuses in the uterus and in some newborn babies. The process of hair growth occurs in distinct sequential stages. The first stage is called ''anagen'' and is the active growth phase, ''telogen'' is the resting stage, ''catagen'' is the regression of the hair follicle phase, ''exogen'' is the active shedding of hair phase and lastly ''kenogen'' is the phase between the empty hair follicle and the growth of new hair. The function of hair in humans has long been a subject of interest ...
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Neural Crest
Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, peripheral and enteric neurons and glia. After gastrulation, neural crest cells are specified at the border of the neural plate and the non-neural ectoderm. During neurulation, the borders of the neural plate, also known as the neural folds, converge at the dorsal midline to form the neural tube. Subsequently, neural crest cells from the roof plate of the neural tube undergo an epithelial to mesenchymal transition, delaminating from the neuroepithelium and migrating through the periphery where they differentiate into varied cell types. The emergence of neural crest was important in vertebrate evolution because many of its structural derivatives are defining features of the vertebrate clade. Underlying the development of neural crest is ...
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TCF7L2
Transcription factor 7-like 2 (T-cell specific, HMG-box), also known as TCF7L2 or TCF4, is a protein acting as a transcription factor that, in humans, is encoded by the ''TCF7L2'' gene. The TCF7L2 gene is located on chromosome 10q25.2–q25.3, contains 19 exons.{ As a member of the TCF family, TCF7L2 can form a bipartite transcription factor and influence several biological pathways, including the Wnt signalling pathway. Single-nucleotide polymorphisms (SNPs) in this gene are especially known to be linked to higher risk to develop type 2 diabetes, gestational diabetes, multiple neurodevelopmental disorders including schizophrenia and autism spectrum disorder, as well as other diseases. The SNP rs7903146, within the TCF7L2 gene, is, to date, the most significant genetic marker associated with type 2 diabetes risk. Function TCF7L2 is a transcription factor influencing the transcription of several genes thereby exerting a large variety of functions within the cell. It is a memb ...
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TCF7L1
Transcription factor 7-like 1, also known as TCF7L1, is a human gene. This gene encodes a member of the T cell factor/lymphoid enhancer factor family of transcription factors. These transcription factors are activated by beta catenin, mediate the Wnt signaling pathway and are antagonized by the transforming growth factor beta signaling pathway. The encoded protein contains a high mobility group-box DNA binding domain and participates in the regulation of cell cycle genes and cellular senescence. Model organisms Model organisms have been used in the study of TCF7L1 function. A conditional knockout mouse line, called ''Tcf7l1tm1a(EUCOMM)Wtsi'' was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty four tests were carried ou ...
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LEF1
Lymphoid enhancer-binding factor 1 (LEF1) is a protein that in humans is encoded by the ''LEF1'' gene. It's a member of T cell factor/lymphoid enhancer factor ( TCF/LEF) family. Function Lymphoid enhancer-binding factor-1 (LEF1) is a 48-kD nuclear protein that is expressed in pre- B and T cells. It binds to a functionally important site in the T-cell receptor-alpha (TCRA) enhancer and confers maximal enhancer activity. LEF1 belongs to a family of regulatory proteins that share homology with high mobility group protein-1 ( HMG1). Clinical significance LEF1 is highly overexpressed and associated with disease progression and poor prognosis in B-cell chronic lymphocytic leukemia and other kinds of malignancies like colorectal cancer. It is also a promising potential drug target. Interactions Lymphoid enhancer-binding factor 1 has been shown to interact with: * ALX4, * AML-1, * Catenin beta-1/β-catenin/''CTNNB1'', including transgenically, * EP300, * MITF * PIAS4, * SMA ...
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TCF7
Transcription factor 7 is the gene that in humans encodes for the TCF1 protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res .... References Further reading

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Nuclear Localisation Sequence
A nuclear localization signal ''or'' sequence (NLS) is an amino acid sequence that 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysines or arginines exposed on the protein surface. Different nuclear localized proteins may share the same NLS. An NLS has the opposite function of a nuclear export signal (NES), which targets proteins out of the nucleus. Types Classical These types of NLSs can be further classified as either monopartite or bipartite. The major structural differences between the two are that the two basic amino acid clusters in bipartite NLSs are separated by a relatively short spacer sequence (hence bipartite - 2 parts), while monopartite NLSs are not. The first NLS to be discovered was the sequence PKKKRKV in the SV40 Large T-antigen (a monopartite NLS). The NLS of nucleoplasmin, KR AATKKAGQAKKK, is the prototype of the ubiquitous bipartite signal: two cluster ...
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High-mobility Group
High-Mobility Group or HMG is a group of chromosomal proteins that are involved in the regulation of DNA-dependent processes such as transcription, replication, recombination, and DNA repair. Families The HMG proteins are subdivided into 3 superfamilies each containing a characteristic functional domain: * HMGA – contains an AT-hook domain ** HMGA1 ** HMGA2 * HMGB – contains a HMG-box domain ** HMGB1 ** HMGB2 ** HMGB3 ** HMGB4 * HMGN – contains a nucleosomal binding domain ** HMGN1 ** HMGN2 ** HMGN3 ** HMGN4 ** HMGN5 Proteins containing any of these embedded in their sequence are known as HMG motif proteins. HMG-box proteins are found in a variety of eukaryotic organisms. They were originally isolated from mammalian cells, and named according to their electrophoretic mobility in polyacrylamide gels. Other families with HMG-box domain * SOX gene family ** Sex-Determining Region Y Protein ** SOX1, SOX2, etc. * TCF/LEF family (T cell factor/lymphoid enhancer factor fa ...
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Sumoylation
In molecular biology, SUMO (Small Ubiquitin-like Modifier) proteins are a family of small proteins that are covalently attached to and detached from other proteins in cells to modify their function. This process is called SUMOylation (sometimes written sumoylation). SUMOylation is a post-translational modification involved in various cellular processes, such as nuclear-cytosolic transport, transcriptional regulation, apoptosis, protein stability, response to stress, and progression through the cell cycle. SUMO proteins are similar to ubiquitin and are considered members of the ubiquitin-like protein family. SUMOylation is directed by an enzymatic cascade analogous to that involved in ubiquitination. In contrast to ubiquitin, SUMO is not used to tag proteins for degradation. Mature SUMO is produced when the last four amino acids of the C-terminus have been cleaved off to allow formation of an isopeptide bond between the C-terminal glycine residue of SUMO and an acceptor lysine o ...
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