ATRX - ویکیپدیا، دانشنامهٔ آزاد
تنظیمکنندهٔ رونویسی ATRX (انگلیسی: ATRX) یا پروتئین هستهای وابسته به کروموزوم ایکس یک پروتئین است که در انسان توسط ژن «ATRX» کُدگذاری میشود.[۵][۶][۷]
این پروتئین یک دومِـین ایتیپاز/هلیکاز دارد و بههمین دلیل عضوی از خانوادهٔ بزرگ SWI/SNF است که بازسازیکننده کروماتین هستند. این پروتئین جهت تغییر مکان هیستون اچ۳ در تلومر و سایر تکرارهای ژنومیک لازم است.[۸] این کار برای فرایند خاموشی ژن در این جایگاههای کروموزومی ضروری است.[۹][۱۰][۱۱]
اهمیت بالینی
[ویرایش]جهشهای ارثی
[ویرایش]جهش های ارثی ژن «ATRX» با سندرم کمتوانی ذهنی آلفا-تالاسمی مرتبط است. طی فرایند پیرایش دگرسان، چند نوع رونویسی مختلف از این ژن شکل میگیرد که منجر به تولید ایزوفرمهای گوناگون از این پروتئین میشود. برخی از زنانی که حامل این تغییرات ژنی هستند، ممکن است دچار اختلال در غیرفعالسازی کروموزوم ایکس شوند.[۷]
جهشهای سوماتیک
[ویرایش]جهشهای اکتسابی این ژن در چندین نوع از سرطانهای انسانی گزارش شده است؛ از جمله در تومورهای نوراندوکرین لوزالمعده،[۱۲] گلیوما،[۱۳][۱۴] استئوسارکوما،[۱۵] سارکوم بافت نرم[۱۶] و فئوکروموسیتوما بدخیم.[۱۷] ارتباط قوی میان جهشهای ژن «ATRX» و فنوتیپ افزایش متناوب طول تلومرها (ALT) در سرطان وجود دارد.[۱۲]
جستارهای وابسته
[ویرایش]منابع
[ویرایش]- ↑ ۱٫۰ ۱٫۱ ۱٫۲ GRCh38: Ensembl release 89: ENSG00000085224 - Ensembl, May 2017
- ↑ ۲٫۰ ۲٫۱ ۲٫۲ GRCm38: Ensembl release 89: ENSMUSG00000031229 - Ensembl, May 2017
- ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ Stayton CL, Dabovic B, Gulisano M, Gecz J, Broccoli V, Giovanazzi S, et al. (November 1994). "Cloning and characterization of a new human Xq13 gene, encoding a putative helicase". Human Molecular Genetics. 3 (11): 1957–64. doi:10.1093/hmg/3.11.1957. PMID 7874112.
- ↑ Gibbons RJ, Suthers GK, Wilkie AO, Buckle VJ, Higgs DR (November 1992). "X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: localization to Xq12-q21.31 by X inactivation and linkage analysis". American Journal of Human Genetics. 51 (5): 1136–49. PMC 1682840. PMID 1415255.
- ↑ ۷٫۰ ۷٫۱ "Entrez Gene: ATRX alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae)".
- ↑ Wong LH, McGhie JD, Sim M, Anderson MA, Ahn S, Hannan RD, et al. (March 2010). "ATRX interacts with H3.3 in maintaining telomere structural integrity in pluripotent embryonic stem cells". Genome Research. 20 (3): 351–60. doi:10.1101/gr.101477.109. PMC 2840985. PMID 20110566.
- ↑ Voon HP, Hughes JR, Rode C, De La Rosa-Velázquez IA, Jenuwein T, Feil R, et al. (April 2015). "ATRX Plays a Key Role in Maintaining Silencing at Interstitial Heterochromatic Loci and Imprinted Genes". Cell Reports. 11 (3): 405–18. doi:10.1016/j.celrep.2015.03.036. PMC 4410944. PMID 25865896.
- ↑ Udugama M, M Chang FT, Chan FL, Tang MC, Pickett HA, R McGhie JD, et al. (December 2015). "Histone variant H3.3 provides the heterochromatic H3 lysine 9 tri-methylation mark at telomeres". Nucleic Acids Research. 43 (21): 10227–37. doi:10.1093/nar/gkv847. PMC 4666390. PMID 26304540.
- ↑ Elsässer SJ, Noh KM, Diaz N, Allis CD, Banaszynski LA (June 2015). "Histone H3.3 is required for endogenous retroviral element silencing in embryonic stem cells". Nature. 522 (7555): 240–4. Bibcode:2015Natur.522..240E. doi:10.1038/nature14345. PMC 4509593. PMID 25938714.
- ↑ ۱۲٫۰ ۱۲٫۱ Heaphy CM, de Wilde RF, Jiao Y, Klein AP, Edil BH, Shi C, et al. (July 2011). "Altered telomeres in tumors with ATRX and DAXX mutations". Science. 333 (6041): 425. Bibcode:2011Sci...333..425H. doi:10.1126/science.1207313. PMC 3174141. PMID 21719641.
- ↑ Schwartzentruber J, Korshunov A, Liu XY, Jones DT, Pfaff E, Jacob K, et al. (January 2012). "Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma". Nature. 482 (7384): 226–31. Bibcode:2012Natur.482..226S. doi:10.1038/nature10833. PMID 22286061. S2CID 4312169.
- ↑ Kannan K, Inagaki A, Silber J, Gorovets D, Zhang J, Kastenhuber ER, et al. (October 2012). "Whole-exome sequencing identifies ATRX mutation as a key molecular determinant in lower-grade glioma". Oncotarget. 3 (10): 1194–203. doi:10.18632/oncotarget.689. PMC 3717947. PMID 23104868.
- ↑ Chen X, Bahrami A, Pappo A, Easton J, Dalton J, Hedlund E, et al. (April 2014). "Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma". Cell Reports. 7 (1): 104–12. doi:10.1016/j.celrep.2014.03.003. PMC 4096827. PMID 24703847.
- ↑ Cancer Genome Atlas Research Network (November 2017). "Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas". Cell. 171 (4): 950–965. doi:10.1016/j.cell.2017.10.014. PMID 29100075.
- ↑ Comino-Méndez, I (June 2016). "ATRX driver mutation in a composite malignant pheochromocytoma". Cancer Genetics. 209 (6): 272–7. doi:10.1016/j.cancergen.2016.04.058. PMID 27209355.
برای مطالعهٔ بیشتر
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