X Kromozomu İnaktivasyonu ve İnaktivasyondan Kaçış

Yıl 2023, Cilt: 32 Sayı: 3, 180 - 187, 30.09.2023

Başak Günaştı

https://doi.org/10.17827/aktd.1319050

Öz

X kromozomunun inaktivasyonu dişi memelilerde iki tane olan X kromozomlarından bir tanesinin inaktive edilmesidir. İnaktivasyona uğrayacak X kromozomu, heterokromatin şeklinde paketlenmektedir. Böylece bu X kromozomunun üzerindeki genlerin eksprese edilmeleri önlenmektedir. İnaktivasyon işlemi, bir adet X kromozomu bulunan erkekler ile iki adet X kromozomu bulunan dişiler arasındaki dengeyi sağlamaktadır. X kromozomu inaktivasyonu, inaktive edilecek tüm X kromozomunda gerçekleştiği düşünülse de, X kromozomunun üzerindeki genlerin tamamı inaktivasyona maruz kalmayıp bir kısmı inaktivasyondan kaçmaktadır. İnsanlarda X kromozomundan kodlanan genlerin yaklaşık %12 ile 20'si kadarı inaktivasyon işleminden kaçarak eksprese olabilmektedir. Derlemede, X inaktivasyonunun mekanizmaları ele alınarak, aktivasyon sürecini ve aktivasyondan kaçan genleri inceleyeceğiz.

Anahtar Kelimeler

X kromozomu , X inaktivasyonu , Dozaj telafisi

Kaynakça

• 1. Chang SC, Tucker T, Thorogood NP, Brown CJ. Mechanisms of X-chromosome inactivation. Front Biosci. 2006;11:852–66.
• 2. Zylicz JJ, Zylicz JJ, Heard E. Molecular mechanisms of facultative heterochromatin formation: An X-chromosome perspective. Annu Rev Biochem. 2020;89:255–82.
• 3. Das N, Rup Singh J, Oza N. Barr bodies in sex determination. J Forensic Dent Sci. 2013;26:5–7.
• 4. Sun Z, Fan J, Wang Y. X-chromosome inactivation and related diseases. Genet Res (Camb). 2022;2022:1-8.
• 5. Patrat C, Ouimette JF, Rougeulle C. X chromosome inactivation in human development. Development. 2020;147:1-13.
• 6. Galupa R, Heard E. X-chromosome inactivation: A crossroads between chromosome architecture and gene regulation. Annu Rev Genet. 2018;52:535–66.
• 7. Panning B. X-chromosome inactivation: The molecular basis of silencing. J Biol. 2008;7:1-13.
• 8. Avner P, Heard E. X-chromosome inactivation: Counting, choice and initiation. Nat Rev Genet. 2001;2:59–67.
• 9. Balaton BP, Brown CJ. Escape artists of the X chromosome. Trends Genet. 2016;32:348–59.
• 10. Heard E, Clerc P, Avner P. X-chromosome inactivation in mammals. Annu Rev Genet. 1997;31:571–610.
• 11. Robert Finestra T, Gribnau J. X chromosome inactivation: silencing, topology and reactivation. Curr Opin Cell Biol. 2017;46:54–61.
• 12. Cantone I, Fisher AG. Human X chromosome inactivation and reactivation: Implications for cell reprogramming and disease. Philos Trans R Soc B Biol Sci. 2017;372:1733-41.
• 13. Wang D, Tang L, Wu Y, Fan C, Zhang S, Xiang B, et al. Abnormal X chromosome inactivation and tumor development. Cell Mol Life Sci. 2020;77:2949–58.
• 14. Brinkman AB, Roelofsen T, Pennings SWC, Martens JHA, Jenuwein T, Stunnenberg HG. Histone modification patterns associated with the human X chromosome. EMBO Rep. 2006;7:628–34.
• 15. Chaumeil J, Okamoto I, Guggiari M, Heard E. Integrated kinetics of X chromosome inactivation in differentiating embryonic stem cells. Cytogenet Genome Res. 2002;99:75–84.
• 16. Shoukat HMH, Ghous G, Tarar ZI, Shoukat MM, Ajmal N. Skewed inactivation of X chromosome: a cause of hemophilia manifestation in carrier females. Cureus. 2020;12:1-10.
• 17. Brown CJ, Greally JM. A stain upon the silence: Genes escaping X inactivation. Trends Genet. 2003;19:432–8.
• 18. Cooper DW. Studies on metatherian sex chromosomes the improbability of a stable balanced polymorphism at an X-linked locus with the paternal X inactivation system of kangaroos. Aust J Biol Sci. 1976;29:245–50.
• 19. Morton WRM, Bishun NP, Rashad MN. The Lyon Hypothesis. Br Med J. 1964;1:840.
• 20. Payer B, Lee JT. X chromosome dosage compensation: How mammals keep the balance. Annu Rev Genet. 2008;42:733–72.
• 21. Navarro-Cobos MJ, Balaton BP, Brown CJ. Genes that escape from X-chromosome inactivation: Potential contributors to Klinefelter syndrome. Am J Med Genet C Semin Med Genet. 2020;184:226–38.
• 22. Lee JT. Lessons from X-chromosome inactivation: Long ncRNA as guides and tethers to the epigenome. Genes Dev. 2009;23:1831–42.
• 23. Galupa R, Heard E. X-chromosome inactivation: New insights into cis and trans regulation. Curr Opin Genet Dev. 2015;31:57–66.
• 24. Lee JT, Lu N. Targeted mutagenesis of Tsix leads to nonrandom X inactivation. Cell. 1999;99:47–57.
• 25. Heard E. Recent advances in X-chromosome inactivation. Curr Opin Cell Biol. 2004;16:247–55.
• 26. Brown CJ, Hendrich BD, Rupert JL, Lafrenière RG, Xing Y, Lawrence J, et al. The human XIST gene: Analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. Cell. 1992;71:527–42.
• 27. Mira-Bontenbal H, Gribnau J. New Xist-interacting proteins in X-chromosome inactivation. Curr Biol. 2016;26:338–42.
• 28. Hong YK, Ontiveros SD, Strauss WM. A revision of the human XIST gene organization and structural comparison with mouse Xist. Mamm Genome. 2000;11:220–4.
• 29. Chadwick BP, Willard HF. Barring gene expression after XIST: Maintaining facultative heterochromatin on the inactive X. Semin Cell Dev Biol. 2003;14:359–67.
• 30. Lee JT, Davidow LS, Warshawsky D. Tsix, a gene antisense to Xist at the X-inactivation centre. Nat Genet. 1999;21:400–4.
• 31. Lv Q, Yuan L, Song Y, Sui T, Li Z, Lai L. D-repeat in the XIST gene is required for X chromosome inactivation. RNA Biol 2016;13:172–6.
• 32. Su Y, Chen X, Zhou H, Shaw S, Chen J, Isales CM, et al. Expression of long noncoding RNA Xist is induced by glucocorticoids. Front Endocrinol (Lausanne). 2022;13:1–12.
• 33. Beard C, Li E, Jaenisch R. Loss of methylation activates Xist in somatic but not in embryonic cells. Genes Dev. 1995;9:2325–34.
• 34. Berletch JB, Yang F, Disteche CM. Escape from X inactivation in mice and humans. Genome Biol. 2010;11:1–7.
• 35. Wutz A, Gribnau J. X inactivation xplained. Curr Opin Genet Dev. 2007;17:387–93.
• 36. Lee JT, Bartolomei MS. X-inactivation, imprinting, and long noncoding RNAs in health and disease. Cell. 2013;152:1308–23.
• 37. Wistuba J. Animal models for Klinefelter’s syndrome and their relevance for the clinic. Mol Hum Reprod. 2010;16:375–85.
• 38. Hatt L, Aagaard MM, Bach C, Graakjaer J, Sommer S, Agerholm IE, et al. Microarray-based analysis of methylation of 1st trimester trisomic placentas from down syndrome, edwards syndrome and patau syndrome. PLoS One. 2016;11:1–11.
• 39. Ben-David U, Amon A. Context is everything: aneuploidy in cancer. Nat Rev Genet. 2020;21:44–62.
• 40. Migeon BR. The role of X inactivation and cellular mosaicism in women’s health and sex-specific diseases. JAMA. 2006;295:1428–33.
• 41. Migeon BR. X inactivation, female mosaicism, and sex differences in renal diseases. J Am Soc Nephrol. 2008;19:2052–9.
• 42. Wang J, Xiao QZ, Chen YM, Yi S, Liu D, Liu YH, et al. DNA hypermethylation and X chromosome inactivation are major determinants of phenotypic variation in women heterozygous for G6PD mutations. Blood Cells, Mol Dis. 2014;53:241–5.
• 43. Errigo A, Bitti A, Galistu F, Salis R, Pes GM, Dore MP. Relationship between Glucose-6-Phosphate Dehydrogenase Deficiency, X-chromosome inactivation and inflammatory markers. Antioxidants (Basel). 2023;12:1–11.
• 44. Agrelo R, Wutz A. Context of change - X inactivation and disease. EMBO Mol Med. 2010;2:6–15.
• 45. Youness A, Miquel CH, Guéry JC. Escape from x chromosome inactivation and the female predominance in autoimmune diseases. Int J Mol Sci. 2021;22:1–12.
• 46. Mousavi MJ, Mahmoudi M, Ghotloo S. Escape from X chromosome inactivation and female bias of autoimmune diseases. Mol Med. 2020;26:1–20.
• 47. Souyris M, Cenac C, Azar P, Daviaud D, Canivet A, Grunenwald S, et al. TLR7 escapes X chromosome inactivation in immune cells. Sci Immunol. 2018;3:1–11.