ATRX
ATRX전사 조절기 ATRX는 ATP 의존 헬리코아제 ATRX, X연계 헬리코아제 II 또는 X연계핵단백질(XNP)이라고도 하며, 인간에서 ATRX 유전자에 의해 인코딩되는 단백질이다.[5][6][7]
함수
전사조절기 ATRX는 ATPase/헬리케아제 도메인을 포함하고 있어 염색질 리모델링 단백질의 SWI/SNF 계열에 속한다.ATRX는 텔로미어 및 기타 게놈 반복에서 히스톤 변종 H3.3의 증착에 필요하다.[8]이러한 상호작용은 이러한 현장의 음소거 유지를 위해 중요하다.[9][10][11]
또한 ATRX는 세포 순환에 의존하는 인산화(phosphysical lation)를 거치게 되는데, 이 인산화 작용은 핵 매트릭스와 염색체 결합을 조절하며, 위상간 유전자 조절과 유사분열에서 염색체 분리에 관여하는 것을 제안한다.[7]
임상적 유의성
상속된 돌연변이
ATRX 유전자의 유전적 돌연변이는 가장 흔히 알파-탈라세미아(ATR-X) 증후군을 동반하는 X-연계 정신지체(XLMR) 증후군과 관련이 있다.이러한 돌연변이는 DNA 메틸화의 패턴에 다양한 변화를 유발하는 것으로 나타났는데, 이는 발달 과정에서 염색질 리모델링, DNA 메틸화, 유전자 발현과 연관성을 제공할 수 있다.구별되는 ISO 양식을 인코딩하는 여러 가지 대안으로 분할된 대본 변형이 보고되었다.여성 캐리어들은 왜곡된 X염색체 비활성화를 보일 수 있다.[7]
체성 돌연변이
ATRX에서 획득한 돌연변이는 췌장 신경내분비 종양,[12] 글리오마,[13] 아스트로사이토마,[14] 골상구균,[15] 악성 페로크로모사이토마 등 다수의 인간암에서 보고됐다.[16]암에서 ATRX 돌연변이와 텔로미어(ALT) 표현형 대안적 연장 사이에는 강한 상관관계가 있다.[12]
상호작용
ATRX는 히스톤 H3.3 샤페론인 DAXX로 콤플렉스를 형성한다.[17]
ATRX는 또한 EZH2와 상호작용하는 것으로 나타났다.[18]
참고 항목
참조
- ^ a b c GRCh38: 앙상블 릴리스 89: ENSG000085224 - 앙상블, 2017년 5월
- ^ a b c GRCm38: 앙상블 릴리스 89: ENSMUSG000031229 - 앙상블, 2017년 5월
- ^ "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.
- ^ a b c "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.
- ^ 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. doi:10.1038/nature14345. PMC 4509593. PMID 25938714.
- ^ 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.
- ^ a b 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. 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. 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.
- ^ 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.
- ^ Lewis PW, Elsaesser SJ, Noh KM, Stadler SC, Allis CD (August 2010). "Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres". Proceedings of the National Academy of Sciences of the United States of America. 107 (32): 14075–80. doi:10.1073/pnas.1008850107. PMC 2922592. PMID 20651253.
- ^ Cardoso C, Timsit S, Villard L, Khrestchatisky M, Fontès M, Colleaux L (April 1998). "Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein". Human Molecular Genetics. 7 (4): 679–84. doi:10.1093/hmg/7.4.679. PMID 9499421.
추가 읽기
- Mulley JC, Kerr B, Stevenson R, Lubs H (1992). "Nomenclature guidelines for X-linked mental retardation". American Journal of Medical Genetics. 43 (1–2): 383–91. doi:10.1002/ajmg.1320430159. PMID 1605216.
- Tang P, Park DJ, Marshall Graves JA, Harley VR (September 2004). "ATRX and sex differentiation". Trends in Endocrinology and Metabolism. 15 (7): 339–44. doi:10.1016/j.tem.2004.07.006. PMID 15350606. S2CID 22192941.
- Forget BG (March 2006). "De novo and acquired forms of alpha thalassemia". Current Hematology Reports. 5 (1): 11–4. PMID 16537041.
- Adès LC, Kerr B, Turner G, Wise G (September 1991). "Smith-Fineman-Myers syndrome in two brothers". American Journal of Medical Genetics. 40 (4): 467–70. doi:10.1002/ajmg.1320400419. PMID 1684092.
- Sutherland GR, Gedeon AK, Haan EA, Woodroffe P, Mulley JC (1988). "Linkage studies with the gene for an X-linked syndrome of mental retardation, microcephaly and spastic diplegia (MRX2)". American Journal of Medical Genetics. 30 (1–2): 493–508. doi:10.1002/ajmg.1320300152. PMID 3177467.
- Shapiro MB, Senapathy P (September 1987). "RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression". Nucleic Acids Research. 15 (17): 7155–74. doi:10.1093/nar/15.17.7155. PMC 306199. PMID 3658675.
- Gibbons RJ, Picketts DJ, Villard L, Higgs DR (March 1995). "Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome)". Cell. 80 (6): 837–45. doi:10.1016/0092-8674(95)90287-2. PMID 7697714.
- Wang LH, Collins A, Lawrence S, Keats BJ, Morton NE (August 1994). "Integration of gene maps: chromosome X". Genomics. 22 (3): 590–604. doi:10.1006/geno.1994.1432. PMID 8001970.
- Gecz J, Pollard H, Consalez G, Villard L, Stayton C, Millasseau P, Khrestchatisky M, Fontes M (January 1994). "Cloning and expression of the murine homologue of a putative human X-linked nuclear protein gene closely linked to PGK1 in Xq13.3". Human Molecular Genetics. 3 (1): 39–44. doi:10.1093/hmg/3.1.39. PMID 8162050.
- Villard L, Gecz J, Mattéi JF, Fontés M, Saugier-Veber P, Munnich A, Lyonnet S (April 1996). "XNP mutation in a large family with Juberg-Marsidi syndrome". Nature Genetics. 12 (4): 359–60. doi:10.1038/ng0496-359. PMID 8630485. S2CID 33759894.
- Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- Picketts DJ, Higgs DR, Bachoo S, Blake DJ, Quarrell OW, Gibbons RJ (December 1996). "ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome". Human Molecular Genetics. 5 (12): 1899–907. doi:10.1093/hmg/5.12.1899. PMID 8968741.
- Villard L, Lacombe D, Fontés M (1997). "A point mutation in the XNP gene, associated with an ATR-X phenotype without alpha-thalassemia". European Journal of Human Genetics. 4 (6): 316–20. doi:10.1159/000472225. PMID 9043863. S2CID 43618843.
- Villard L, Lossi AM, Cardoso C, Proud V, Chiaroni P, Colleaux L, Schwartz C, Fontés M (July 1997). "Determination of the genomic structure of the XNP/ATRX gene encoding a potential zinc finger helicase". Genomics. 43 (2): 149–55. doi:10.1006/geno.1997.4793. PMID 9244431.
- Golub EI, Kovalenko OV, Gupta RC, Ward DC, Radding CM (October 1997). "Interaction of human recombination proteins Rad51 and Rad54". Nucleic Acids Research. 25 (20): 4106–10. doi:10.1093/nar/25.20.4106. PMC 147015. PMID 9321665.
- Gibbons RJ, Bachoo S, Picketts DJ, Aftimos S, Asenbauer B, Bergoffen J, Berry SA, Dahl N, Fryer A, Keppler K, Kurosawa K, Levin ML, Masuno M, Neri G, Pierpont ME, Slaney SF, Higgs DR (October 1997). "Mutations in transcriptional regulator ATRX establish the functional significance of a PHD-like domain". Nature Genetics. 17 (2): 146–8. doi:10.1038/ng1097-146. PMID 9326931. S2CID 12470300.
- Cardoso C, Timsit S, Villard L, Khrestchatisky M, Fontès M, Colleaux L (April 1998). "Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein". Human Molecular Genetics. 7 (4): 679–84. doi:10.1093/hmg/7.4.679. PMID 9499421.
- Bérubé NG, Mangelsdorf M, Jagla M, Vanderluit J, Garrick D, Gibbons RJ, Higgs DR, Slack RS, Picketts DJ (February 2005). "The chromatin-remodeling protein ATRX is critical for neuronal survival during corticogenesis". The Journal of Clinical Investigation. 115 (2): 258–67. doi:10.1172/JCI22329. PMC 544602. PMID 15668733.
외부 링크
- GeneReviews/NCBI/NIH/UW entry on Alpha-Thalaxia X-Linked 정신지체증후군; ATRX 증후군; Alpha Thalasia/정신지체증, X-Linked; XLMR-Hypotonic Face Syndrome
- 알파-탈라세미아 X-연계 정신지체 증후군에 대한 OMIM 항목
- UCSC 게놈 브라우저의 인간 ATRX 게놈 위치 및 ATRX 유전자 세부 정보 페이지.
- UCSC 게놈 브라우저의 인간 RAD54L 게놈 위치 및 RAD54L 유전자 세부 정보 페이지.