SNAI1
Description
The SNAI1 (snail family transcriptional repressor 1) is a protein-coding gene located on chromosome 20.
Zinc finger protein SNAI1 (sometimes referred to as Snail) is a protein that in humans is encoded by the SNAI1 gene. Snail is a family of transcription factors that promote the repression of the adhesion molecule E-cadherin to regulate epithelial to mesenchymal transition (EMT) during embryonic development.
== Function == The Drosophila embryonic protein SNAI1, commonly known as Snail, is a zinc finger transcriptional repressor which downregulates the expression of ectodermal genes within the mesoderm. The nuclear protein encoded by this gene is structurally similar to the Drosophila Snail protein, and is also thought to be critical for mesoderm formation in the developing embryo. At least two variants of a similar processed pseudogene have been found on chromosome 2. SNAI1 zinc-fingers (ZF) binds to E-box, an E-cadherin promoter region, and represses the expression of the adhesion molecule, which induces the tightly bound epithelial cells to break loose from each other and migrate into the developing embryo to become mesenchymal cells. This process allows for the formation of the mesodermal layer in the developing embryo. Though SNAI1 is shown to repress expression of E-cadherin in epithelial cells, studies have shown homozygous mutant embryos are still able to form a mesodermal layer. However, the mesodermal layer present shows characteristics of epithelial cells and not mesenchymal cells (the mutant mesoderm cells exhibited a polarized state). Other studies show that mutation of specific ZFs contribute to a decrease in SNAI1 E-cadherin repression.
SNAI1 plays a crucial role in various cellular processes, including epithelial to mesenchymal transition (EMT), embryonic mesoderm formation and maintenance, growth arrest, survival, and cell migration. It binds to specific DNA sequences called E-boxes located within the promoter regions of genes like E-cadherin/CDH1, CLDN7, and KRT8, effectively repressing their transcription. This repression is achieved by working in concert with histone demethylase KDM1A, which SNAI1 recruits to these promoters. Together, they cause a decrease in dimethylated H3K4 levels, a modification associated with active gene transcription. Additionally, SNAI1's SNAG domain competes with histone H3 for binding to the KDM1A-RCOR1 histone demethylase complex, hindering the demethylation of histone H3 at Lys-4. During EMT, SNAI1 collaborates with LOXL2 to negatively regulate pericentromeric heterochromatin transcription. SNAI1 guides LOXL2 to these regions, where it oxidizes histone H3 and represses transcription, ultimately leading to the release of the heterochromatin component CBX5/HP1A. This process facilitates chromatin reorganization and the acquisition of mesenchymal traits. SNAI1 can associate with EGR1 and SP1 to mediate the upregulation of CDKN2B in response to tetradecanoyl phorbol acetate (TPA) stimulation. It is thought to achieve this by binding to the CDKN2B promoter region at the 5'-TCACA-3' sequence. Moreover, SNAI1 may also directly activate the CDKN2B promoter independently.
SNAI1 is also known as SLUGH2, SNA, SNAH, SNAIL, SNAIL1, dJ710H13.1.
