Molecular Development - X Inactivation: Difference between revisions
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:'''Links:''' [http://www.ncbi.nlm.nih.gov/omim/314670 OMIM - Xist] | |||
==X Inactivation (xist) History== | ==X Inactivation (xist) History== |
Revision as of 07:51, 22 November 2010
Introduction
The presence in females of 2 X chromosome raises the issue of gene dosage, in the case of mammals this is regulated by inactivating one of the X chromosomes. To balance expression with the autosomal chromosomes the dosage imbalance is then adjusted by doubling expression of X-linked genes in both sexes.
In some other species compensation occurs by increasing the expression of X in males. The pattern of which X chromosome is inactivated in cells appears to be random, generating 50% cells expressing Father X, 50% cells expressing Mother X (mosaic pattern). The theory of random X inactivation was first suggested in mice in 1961.[2]
The process of inactivation relies on the Xist RNA, a 17 kb non-coding RNA, which accumulates on the future inactive X chromosome.
A second form of X inactivation that occurs only in male meiotic spermatogenesis, meiotic sex chromosome inactivation (MSCI), is not covered in these current notes. MSCI is the process of transcriptional silencing of the X and Y chromosomes.[3]
Some Recent Findings
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X inactivation Xist
- Links: OMIM - Xist
X Inactivation (xist) History
The theory of random X inactivation was first suggested in mice in 1961.[2] The breakthrough was the discovery of the X inactive specific transcript (XIST). [6] This gene is located within the "X inactivation centre" and only expressed by the inactive X chromosome. unlike other genes that encode protein XIST contained no "open reading frames" (ie no codons to encode amino acids). XIST is transcribed but not translated. XIST appears to act as RNA. Current thinking is that it binds to the X Chromosome and is involved in it's translocation to the nuclear periphery. It now appears that XIST appears to initiate X inactivation and it is the methylation of the inactive X genes that maintains inactivity.
Tsix
A gene antisense to Xist, hence the name which is Xist backwards, in embryonic stem cells Xist repression occurs and Tsix is upregulated. This is part of the overall process of maintaining pluripotency in these cells. Tsix upregulation depends on the recruitment of another pluripotent marker Rex1, and of the associated factors Klf4 and c-Myc, by the DXPas34 minisatellite associated with the Tsix promoter.[7]
- Links: OMIM - Tsix
Meiotic Sex Chromosome Inactivation
This second form of X inactivation takes place in the male, during spermatogenesis, as germ cells enter meiosis. This is thought to be a form of meiotic silencing of unsynapsed chromatin that silences chromosomes that fail to pair with their homologous partners.[8]
References
Search Pubmed
July 2010 "X Inactivation" - All (3157) Review (519) Free Full Text (1066)
Search Pubmed Now: X Inactivation
Glossary Links
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Cite this page: Hill, M.A. (2024, June 15) Embryology Molecular Development - X Inactivation. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Molecular_Development_-_X_Inactivation
- © Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G