UNSW Embryology

Week 1 X Inactivation (xist)

© Dr Mark Hill (2009)

Acknowledgements

X Inactivation (xist)

X- Chromosome

• Contains about 5% of the haploid genome.
• Genes encode house-keeping and specialized functions.
• Completely conserved in gene content between species.
• It does not encode sex determination or differentiation.
• In females one of the X-chromosomes is inactivated in each and every cell. [known since 1961]
• This inactivation occurs during embryogenesis.
• X Inactivation appears to be random in somatic cells. (mosaic pattern)
• The process starts at the "X inactivation centre" and spreads along the chromosome.
• The mechanism of inactivation was unknown.

X Inactivation (xist) History

• The breakthrough was the discovery of the X inactive specific transcript (XIST). Brown et. al., (1991) Nature 349, 372-373.
• 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.

References

• A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Brown CJ, Ballabio A, Rupert JL, Lafreniere RG, Grompe M, Tonlorenzi R, Willard HFNature 1991 Jan 3;349(6304):38-44 Abstract
• Localization of the X inactivation centre on the human X chromosome in Xq13. Brown CJ, Lafreniere RG, Powers VE, Sebastio G, Ballabio A, Pettigrew AL, Ledbetter DH, Levy E, Craig IW, Willard HF Nature 1991 Jan 3;349(6304):82-4 Abstract
• X-chromosome inactivation in mammals. Heard E, Clerc P, Avner P Annu Rev Genet 1997;31:571-610 (review article) Abstract
• Epigenetic programming of differential gene expression in development and evolution. Monk M Dev Genet 1995;17(3):188-97 Abstract

Quick Links

Week 1 Pages:

Introduction | Abnormalities | Gamete formation | Cell division | Fertilization | Zygote | Blastocyst | Male sex determination| X inactivation | References | Text only page | WWW Links |

Development Notes ----------------- Menstrual Cycle Week 1 Week 2 Week 3 Week 4 Placenta Serial Images Genes/DNA Molecular Dev Abnormal Dev Postnatal Dev Notes Index

System Notes ----------------- Heart/Cardiovascular Respiratory Coelomic cavity Gastrointestinal Tract Head and Neck Neural Neural Crest Eye Ear Nose Endocrine Urogenital Musculoskeletal Integumentary

Movies ----------------- Embryo Growth Ultrasound Week 1 Week 2 Week 3 Week 4 Stage 13/14 Stage 22 Neural Head and Neck Heart Vasculature Gastrointestinal Urogenital Other Embryos Larsen Internet

Other Embryos ----------------- Chicken Fly Frog Mouse Rabbit Rat Worm Zebrafish Guinea Pig

UNSW Embryology ISBN: 978 0 7334 2609 4

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