User:Swx468/sandbox

This article was the subject of an educational assignment in 2014 Q3. Further details were available on the "Education Program:University of Western Ontario/Advanced Genetics (Fall 2014)" page, which is now unavailable on the wiki.

My choosen topic is SOX9. It was previously a very short article that I have added on to. I will be working on this alone. Hopefullly this is an acceptable topic? Please let me know if it isn't, I can work on another one instead if necessary. Thanks!

Transcription factor SOX-9 is a protein that in humans is encoded by the 5,401 bases long SOX9 gene ^[1][2] located on the q arm of chromosome 17 in band 24.3. It encompasses bases 70,117,161 bp from P-ter to 70,122,561 bp from P-ter.^[3] This transcription factor recognizes the binding site “CCTTGAG” in genomic DNA. It is involved in chondrocyte differentiation, testis determination, as well as the differentiation of several other tissues during development. Mutations affecting this gene generally lead to campomelic dysplasia, and sometimes even sex reversal.

Like the other genes in the Sox (Sry-related HMG box) family, it contains a HMG (high mobility) box domain (a conserved 79 amino acid (AA) high-efficiency DNA binding domain). It also contains a dimerization domain at the N-terminal, and two transactivation domains (in the central position and the C terminal). ^[4] Its transcription is enhanced by SRY binding to a testis-specific enhancer of Sox9 (TES), which activates Sox9 and SF1 expression during embryogenesis. ^[5] The protein product bind to the minor groove of genomic DNA, which causes the DNA to bend 60-85°. Sox9 transcription factor can upregulate or downregulate the transcription of specific genes, thereby regulate differentiation and maintenance of certain cell types and tissues.

SOX-9 recognizes the sequence CCTTGAG along with other members of the HMG-box class DNA-binding proteins. It acts during chondrocyte differentiation and, with steroidogenic factor 1, regulates transcription of the anti-Müllerian hormone (AMH) gene.^[2]

SOX9 (located on chromosome 17) is the main target of SRY protein. Transcription of SOX9 is promoted when TDF binds to testis specific enhancer (TES) upstream of SOX9 gene. This gene is shown to be necessary for testis determination during development. Unlike SRY, SOX9 is shown to be expressed passed embryonic development in mice. This suggests that SOX9 also plays a role in the gonads to recruit somatic gonadal cells to become sertoli cells in adult organisms. In addition, expression of SOX9 seems to only need to be stimulated by SRY as it uses an auto-regulatory positive-feedback loop (by assiociating with FGF9^[6] and PGD2) to promote its own continued expression (by binding to TES). ^[7] Activation of FGF9 by SOX-9 starts vital processes in male development, such as the creation of testis cords and the multiplication of Sertoli cells.^[6] The association of SOX-9 and Dax1 creates Sertoli cells, another vital process in male development.^[8] SOX-9 also plays a pivotal role in male sexual development by working with Sf1, SOX-9 can produce AMH in Sertoli cells to inhibit the creation of a female reproductive system.^[9] It also interacts with a few other genes to promote the development of male sexual organs.

Sox9 is expressed in the genital ridge at 10.5 days post fertilization (before the expression of SRY). In male embryos, Sry expression peaks at 11.5 days, subsequently Sox9 expression significantly increases. In contrast, in XX embryos, Sox9 expression decreases. The high levels of Sox9 causes pre-gonadal ridge cells to differentiate into Sertoli cells rather than granulosa cells. Knock-out of the Sox9 gene in XY embryo results in development of ovaries instead of testis. ^[10]

SOX9 also functions during human pancreatic development. At first, SOX9 is expressed in all epithelial tissue in the pancreas during early development. However its expression is later confined to only the ductal and centroacinar cells (ie the endocrine cells). The expression of SOX9 in pancreatic cells is regulated by FGF and Notch signaling pathways. As well, its continued expression is maintained by the Fgf10/Fgfr2b/Sox9 feed-forward loop (in which Fgfr2b is a receptor whose transcription is increased by SOX9 and transduces a Fgf10 signal, Fgf10 upregulates SOX9. ^[11] Mature differentiated acinar and endocrine cells do not express SOX9.

Similarly, during duodenal development, SOX9 is expressed in all epithelial cells of the duodenum. By adulthood, it is only found in the crypts of Lieberkühn at base of mucosal folds.^[12]

Mutations lead to the skeletal malformation syndrome campomelic dysplasia. This disorder also affects the reproductive system, and other parts of the body. Approximately 5% of cases arise from a mutation near the SOX9 gene, the rest are caused by a mutation on the gene itself. This disorder is often fatal in newborns.^[13] Another disorder that is related to abnormal regulation of SOX9 is isolated Pierre Robin sequence. Symptoms of this disorder are micrognathia (small lower jaw), glossoptosis (tongue that is further back in the mouth), and a cleft palate.^[14] These symptoms manifest because SOX9 is involved in the development of the skeletal system, including the manible. In some cases, misregulation of SOX9 can lead to autosomal sex reversal. If an XX individual gains an extra SOX9 gene, they will develop as males even in the absence of SRY. ^[15]

SOX9 has been shown to interact with Steroidogenic factor 1,^[9] MED12^[16] and MAF.^[17]

• SOX genes

• SOX9+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• SOX9 human gene location in the UCSC Genome Browser.
• SOX9 human gene details in the UCSC Genome Browser.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Category:Transcription factors