Tsix
Tsix is a gene that functions as the antisense to the Xist gene during X chromosome inactivation.[1] Tsix controls X chromosome inactivation by preventing the accumulation of Xist on one female X chromosome to maintain the active euchromatic state of the chosen chromosome.
Function in mice
In mice and some other mammals, the maternal X chromosome is always active and the paternal X chromosome is always silenced, in a process called imprinting. Tsix functions here to bind complementary Xist RNA and render it non-functional. Thus, Xist does not condense chromatin on the maternal chromosome, letting it remain active. This does not occur on the paternal chromosome, and thus Xist proceeds to inactivate that chromosome. [2] Tsix regulates X chromosome dosage compensation in female mice to prevent early embryonic mortality by a dual dose of X-linked genes.[3] Tsix allows for equal dosage of X-linked genes for both males and females by inactivating the extra X chromosome in the females.[4] The mutation of genes on maternal Tsix can cause over accumulation of Xist on both X chromosomes and cause early lethality of embryo as the two X chromosomes in females and the single X chromosome in male becomes inadvertently inactivated. However, if the paternal Tsix allele is active, it can rescue female embryos from the over-accumulation of Xist.[5]
Tsix in humans
X chromosome inactivation is random in human females, and imprinting does not occur. The deletion of a CpG island in the human Tsix gene prevents Tsix from imprinting on the X chromosomes. Instead, the human Tsix chromosome is coexpressed with the human Xist gene on the inactivated X chromosome, indicating that it does not play an important role in random X chromosome inactivation. [6] The presence of Tsix in humans may be an evolutionary vestige. Alternately, it may be necessary to study cells closer to the X inactivation stage rather than older cells in order to accurately locate Tsix expression and function. [7]
References
- ^ Lee, JT, LS Davidow, D. Warshawsky, and Nat Genet. "Tsix, a Gene Antisense to Xist at the X-inactivation Centre." NCBI. U.S. National Library of Medicine, 21 Apr. 1999. Web. 20 Mar. 2013. <http://www.ncbi.nlm.nih.gov/m/pubmed/10192391>.
- ^ Cobb, K. ""Not a turn-on" Science News. August 17, 2002. p100-101.
- ^ "Tsix MGI Mouse Gene Detail." Mouse Genome Informatics. The Jackson Laboratory, n.d. Web. 20 Mar. 2013. <http://www.informatics.jax.org/marker/MGI:1336196>.
- ^ Stavropoulos, Nicholas, Naifung Lu, and Jeannie T. Lee. "A Functional Role for Tsix Transcription in Blocking Xist RNA Accumulation but Not in X-chromosome Choice." A Functional Role for Tsix Transcription in Blocking Xist RNA Accumulation but Not in X-chromosome Choice. Ed. Stanley M. Gartler. Proceedings of the National Academy of Sciences of the United States of America, 8 June 2001. Web. 20 Mar. 2013. <http://www.pnas.org/content/98/18/10232.long>.
- ^ Sado, T., Z. Wang, H. Sasaki, and E. Li. "Regulation of Imprinted X-chromosome Inactivation in Mice by Tsix." NCBI. U.S. National Library of Medicine, Apr. 2001. Web. 20 Mar. 2013. <http://www.ncbi.nlm.nih.gov/m/pubmed/11262229>.
- ^ Migeon, Barbara R. "Is Tsix Repression of Xist Specific to Mouse?" Nature.com. Nature Publishing Group, 2003. Web. 20 Mar. 2013. An autosome may be a more likely candidate for regulating this process in humans. <http://www.nature.com/ng/journal/v33/n3/full/ng0303-337a.html>.
- ^ Cobb, K. ""Not a turn-on" Science News. August 17, 2002. p100-101.