BRM-SWI/SNF chromatin remodeling complex enables functional telomeres by promoting co-expression of TRF2 and TRF1


Autoři: Shu Wu aff001;  Yuanlong Ge aff002;  Xiaocui Li aff001;  Yiding Yang aff001;  Haoxian Zhou aff001;  Kaixuan Lin aff003;  Zepeng Zhang aff002;  Yong Zhao aff001
Působiště autorů: MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China aff001;  Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou, China aff002;  Yale Stem Cell Center & Department of Genetics, Yale School of Medicine, New Haven, Connecticut, United States of America aff003
Vyšlo v časopise: BRM-SWI/SNF chromatin remodeling complex enables functional telomeres by promoting co-expression of TRF2 and TRF1. PLoS Genet 16(6): e32767. doi:10.1371/journal.pgen.1008799
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008799

Souhrn

TRF2 and TRF1 are a key component in shelterin complex that associates with telomeric DNA and protects chromosome ends. BRM is a core ATPase subunit of SWI/SNF chromatin remodeling complex. Whether and how BRM-SWI/SNF complex is engaged in chromatin end protection by telomeres is unknown. Here, we report that depletion of BRM does not affect heterochromatin state of telomeres, but results in telomere dysfunctional phenomena including telomere uncapping and replication defect. Mechanistically, expression of TRF2 and TRF1 is jointly regulated by BRM-SWI/SNF complex, which is localized to promoter region of both genes and facilitates their transcription. BRM-deficient cells bear increased TRF2-free or TRF1-free telomeres due to insufficient expression. Importantly, BRM depletion-induced telomere uncapping or replication defect can be rescued by compensatory expression of exogenous TRF2 or TRF1, respectively. Together, these results identify a new function of BRM-SWI/SNF complex in enabling functional telomeres for maintaining genome stability.

Klíčová slova:

Apoptosis – Gene expression – Genome complexity – HeLa cells – Chromatin – Micronuclei – Small interfering RNAs – Telomeres


Zdroje

1. Shay JW, Wright WE. Telomeres and telomerase in normal and cancer stem cells. FEBS letters. 2010;584(17):3819–25. Epub 2010/05/25. doi: 10.1016/j.febslet.2010.05.026 20493857; PubMed Central PMCID: PMC3370416.

2. de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005;19(18):2100–10. Epub 2005/09/17. doi: 10.1101/gad.1346005 16166375.

3. de Lange T. Shelterin-Mediated Telomere Protection. Annu Rev Genet. 2018;52:223–47. Epub 2018/09/13. doi: 10.1146/annurev-genet-032918-021921 30208292.

4. Karlseder J, Broccoli D, Dai Y, Hardy S, de Lange T. p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science. 1999;283(5406):1321–5. Epub 1999/02/26. doi: 10.1126/science.283.5406.1321 10037601.

5. van Steensel B, Smogorzewska A, de Lange T. TRF2 protects human telomeres from end-to-end fusions. Cell. 1998;92(3):401–13. Epub 1998/02/26. doi: 10.1016/s0092-8674(00)80932-0 9476899.

6. Sfeir A, Kosiyatrakul ST, Hockemeyer D, MacRae SL, Karlseder J, Schildkraut CL, et al. Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication. Cell. 2009;138(1):90–103. Epub 2009/07/15. doi: 10.1016/j.cell.2009.06.021 19596237; PubMed Central PMCID: PMC2723738.

7. Takai KK, Hooper S, Blackwood S, Gandhi R, de Lange T. In vivo stoichiometry of shelterin components. J Biol Chem. 2010;285(2):1457–67. Epub 2009/10/30. doi: 10.1074/jbc.M109.038026 19864690; PubMed Central PMCID: PMC2801271.

8. Dong W, Shen R, Wang Q, Gao Y, Qi X, Jiang H, et al. Sp1 upregulates expression of TRF2 and TRF2 inhibition reduces tumorigenesis in human colorectal carcinoma cells. Cancer Biol Ther. 2009;8(22):2166–74. Epub 2009/09/29. doi: 10.4161/cbt.8.22.9880 19783902.

9. Diala I, Wagner N, Magdinier F, Shkreli M, Sirakov M, Bauwens S, et al. Telomere protection and TRF2 expression are enhanced by the canonical Wnt signalling pathway. EMBO reports. 2013;14(4):356–63. Epub 2013/02/23. doi: 10.1038/embor.2013.16 23429341; PubMed Central PMCID: PMC3615653.

10. Luo Z, Feng X, Wang H, Xu W, Zhao Y, Ma W, et al. Mir-23a induces telomere dysfunction and cellular senescence by inhibiting TRF2 expression. Aging cell. 2015;14(3):391–9. Epub 2015/03/11. doi: 10.1111/acel.12304 25753893; PubMed Central PMCID: PMC4406668.

11. Dinami R, Ercolani C, Petti E, Piazza S, Ciani Y, Sestito R, et al. miR-155 drives telomere fragility in human breast cancer by targeting TRF1. Cancer research. 2014;74(15):4145–56. Epub 2014/05/31. doi: 10.1158/0008-5472.CAN-13-2038 24876105.

12. Wilson BG, Roberts CW. SWI/SNF nucleosome remodellers and cancer. Nat Rev Cancer. 2011;11(7):481–92. Epub 2011/06/10. doi: 10.1038/nrc3068 21654818.

13. Kadoch C, Crabtree GR. Mammalian SWI/SNF chromatin remodeling complexes and cancer: Mechanistic insights gained from human genomics. Science advances. 2015;1(5):e1500447. Epub 2015/11/26. doi: 10.1126/sciadv.1500447 26601204; PubMed Central PMCID: PMC4640607.

14. Phelan ML, Sif S, Narlikar GJ, Kingston RE. Reconstitution of a core chromatin remodeling complex from SWI/SNF subunits. Molecular cell. 1999;3(2):247–53. Epub 1999/03/17. doi: 10.1016/s1097-2765(00)80315-9 10078207.

15. Wu S, Ge Y, Huang L, Liu H, Xue Y, Zhao Y. BRG1, the ATPase subunit of SWI/SNF chromatin remodeling complex, interacts with HDAC2 to modulate telomerase expression in human cancer cells. Cell Cycle. 2014;13(18):2869–78. Epub 2014/12/09. doi: 10.4161/15384101.2014.946834 25486475; PubMed Central PMCID: PMC4612678.

16. Pruitt SC, Qin M, Wang J, Kunnev D, Freeland A. A Signature of Genomic Instability Resulting from Deficient Replication Licensing. PLoS genetics. 2017;13(1):e1006547. Epub 2017/01/04. doi: 10.1371/journal.pgen.1006547 28045896; PubMed Central PMCID: PMC5242545.

17. Postepska-Igielska A, Krunic D, Schmitt N, Greulich-Bode KM, Boukamp P, Grummt I. The chromatin remodelling complex NoRC safeguards genome stability by heterochromatin formation at telomeres and centromeres. EMBO Rep. 2013;14(8):704–10. Epub 2013/06/26. doi: 10.1038/embor.2013.87 23797874; PubMed Central PMCID: PMC3736129.

18. Marechal A, Zou L. DNA damage sensing by the ATM and ATR kinases. Cold Spring Harbor perspectives in biology. 2013;5(9). Epub 2013/09/05. doi: 10.1101/cshperspect.a012716 24003211; PubMed Central PMCID: PMC3753707.

19. Denchi EL, de Lange T. Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1. Nature. 2007;448(7157):1068–71. Epub 2007/08/10. doi: 10.1038/nature06065 17687332.

20. Mailand N, Gibbs-Seymour I, Bekker-Jensen S. Regulation of PCNA-protein interactions for genome stability. Nat Rev Mol Cell Biol. 2013;14(5):269–82. Epub 2013/04/19. doi: 10.1038/nrm3562 23594953.

21. Bhat KP, Cortez D. RPA and RAD51: fork reversal, fork protection, and genome stability. Nat Struct Mol Biol. 2018;25(6):446–53. Epub 2018/05/29. doi: 10.1038/s41594-018-0075-z 29807999; PubMed Central PMCID: PMC6006513.

22. Takai H, Smogorzewska A, de Lange T. DNA damage foci at dysfunctional telomeres. Curr Biol. 2003;13(17):1549–56. Epub 2003/09/06. doi: 10.1016/s0960-9822(03)00542-6 12956959.

23. Raab JR, Runge JS, Spear CC, Magnuson T. Co-regulation of transcription by BRG1 and BRM, two mutually exclusive SWI/SNF ATPase subunits. Epigenetics Chromatin. 2017;10(1):62. Epub 2017/12/24. doi: 10.1186/s13072-017-0167-8 29273066; PubMed Central PMCID: PMC5740901.

24. Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic acids research. 2017;45(W1):W98–w102. Epub 2017/04/14. doi: 10.1093/nar/gkx247 28407145; PubMed Central PMCID: PMC5570223.

25. Felsenfeld G, Groudine M. Controlling the double helix. Nature. 2003;421(6921):448–53. Epub 2003/01/24. doi: 10.1038/nature01411 12540921.

26. Berger SL. The complex language of chromatin regulation during transcription. Nature. 2007;447(7143):407–12. Epub 2007/05/25. doi: 10.1038/nature05915 17522673.

27. Hargreaves DC, Crabtree GR. ATP-dependent chromatin remodeling: genetics, genomics and mechanisms. Cell Res. 2011;21(3):396–420. Epub 2011/03/02. doi: 10.1038/cr.2011.32 21358755; PubMed Central PMCID: PMC3110148.

28. Helming KC, Wang X, Roberts CWM. Vulnerabilities of mutant SWI/SNF complexes in cancer. Cancer cell. 2014;26(3):309–17. Epub 2014/09/10. doi: 10.1016/j.ccr.2014.07.018 25203320; PubMed Central PMCID: PMC4159614.

29. Ribeiro-Silva C, Aydin OZ, Mesquita-Ribeiro R, Slyskova J, Helfricht A, Marteijn JA, et al. DNA damage sensitivity of SWI/SNF-deficient cells depends on TFIIH subunit p62/GTF2H1. Nat Commun. 2018;9(1):4067. Epub 2018/10/06. doi: 10.1038/s41467-018-06402-y 30287812; PubMed Central PMCID: PMC6172278.

30. Schick S, Rendeiro AF, Runggatscher K, Ringler A, Boidol B, Hinkel M, et al. Systematic characterization of BAF mutations provides insights into intracomplex synthetic lethalities in human cancers. Nat Genet. 2019;51(9):1399–410. Epub 2019/08/21. doi: 10.1038/s41588-019-0477-9 31427792; PubMed Central PMCID: PMC6952272.

31. Varela E, Schneider RP, Ortega S, Blasco MA. Different telomere-length dynamics at the inner cell mass versus established embryonic stem (ES) cells. Proc Natl Acad Sci U S A. 2011;108(37):15207–12. Epub 2011/08/30. doi: 10.1073/pnas.1105414108 21873233; PubMed Central PMCID: PMC3174656.

32. Karlseder J, Kachatrian L, Takai H, Mercer K, Hingorani S, Jacks T, et al. Targeted deletion reveals an essential function for the telomere length regulator Trf1. Mol Cell Biol. 2003;23(18):6533–41. Epub 2003/08/29. doi: 10.1128/mcb.23.18.6533-6541.2003 12944479; PubMed Central PMCID: PMC193696.

33. Ovando-Roche P, Yu JS, Testori S, Ho C, Cui W. TRF2-mediated stabilization of hREST4 is critical for the differentiation and maintenance of neural progenitors. Stem Cells. 2014;32(8):2111–22. Epub 2014/04/18. doi: 10.1002/stem.1725 24740933.

34. Lobanova A, She R, Pieraut S, Clapp C, Maximov A, Denchi EL. Different requirements of functional telomeres in neural stem cells and terminally differentiated neurons. Genes Dev. 2017;31(7):639–47. Epub 2017/04/22. doi: 10.1101/gad.295402.116 28428263; PubMed Central PMCID: PMC5411705.

35. Strobeck MW, Reisman DN, Gunawardena RW, Betz BL, Angus SP, Knudsen KE, et al. Compensation of BRG-1 function by Brm: insight into the role of the core SWI-SNF subunits in retinoblastoma tumor suppressor signaling. J Biol Chem. 2002;277(7):4782–9. Epub 2001/11/24. doi: 10.1074/jbc.M109532200 11719516.

36. Flowers S, Nagl NG Jr., Beck GR Jr., Moran E. Antagonistic roles for BRM and BRG1 SWI/SNF complexes in differentiation. J Biol Chem. 2009;284(15):10067–75. Epub 2009/01/16. doi: 10.1074/jbc.M808782200 19144648; PubMed Central PMCID: PMC2665061.

37. Hohmann AF, Vakoc CR. A rationale to target the SWI/SNF complex for cancer therapy. Trends Genet. 2014;30(8):356–63. Epub 2014/06/17. doi: 10.1016/j.tig.2014.05.001 24932742; PubMed Central PMCID: PMC4112150.

38. Brownlee PM, Meisenberg C, Downs JA. The SWI/SNF chromatin remodelling complex: Its role in maintaining genome stability and preventing tumourigenesis. DNA Repair (Amst). 2015;32:127–33. Epub 2015/05/20. doi: 10.1016/j.dnarep.2015.04.023 25981841.

39. Savas S, Skardasi G. The SWI/SNF complex subunit genes: Their functions, variations, and links to risk and survival outcomes in human cancers. Critical reviews in oncology/hematology. 2018;123:114–31. Epub 2018/02/28. doi: 10.1016/j.critrevonc.2018.01.009 29482773.

40. Masliah-Planchon J, Bieche I, Guinebretiere JM, Bourdeaut F, Delattre O. SWI/SNF chromatin remodeling and human malignancies. Annual review of pathology. 2015;10:145–71. Epub 2014/11/12. doi: 10.1146/annurev-pathol-012414-040445 25387058.

41. Ribeiro-Silva C, Vermeulen W, Lans H. SWI/SNF: Complex complexes in genome stability and cancer. DNA Repair (Amst). 2019;77:87–95. Epub 2019/03/22. doi: 10.1016/j.dnarep.2019.03.007 30897376.

42. Watanabe R, Ui A, Kanno S, Ogiwara H, Nagase T, Kohno T, et al. SWI/SNF factors required for cellular resistance to DNA damage include ARID1A and ARID1B and show interdependent protein stability. Cancer research. 2014;74(9):2465–75. Epub 2014/05/03. doi: 10.1158/0008-5472.CAN-13-3608 24788099.

43. Ogiwara H, Ui A, Otsuka A, Satoh H, Yokomi I, Nakajima S, et al. Histone acetylation by CBP and p300 at double-strand break sites facilitates SWI/SNF chromatin remodeling and the recruitment of non-homologous end joining factors. Oncogene. 2011;30(18):2135–46. Epub 2011/01/11. doi: 10.1038/onc.2010.592 21217779.

44. Wu P, de Lange T. No overt nucleosome eviction at deprotected telomeres. Mol Cell Biol. 2008;28(18):5724–35. Epub 2008/07/16. doi: 10.1128/MCB.01764-07 18625717; PubMed Central PMCID: PMC2546919.

45. Afgan E, Baker D, Batut B, van den Beek M, Bouvier D, Cech M, et al. The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2018 update. Nucleic acids research. 2018;46(W1):W537–w44. Epub 2018/05/24. doi: 10.1093/nar/gky379 29790989; PubMed Central PMCID: PMC6030816.

46. Robinson JT, Thorvaldsdottir H, Wenger AM, Zehir A, Mesirov JP. Variant Review with the Integrative Genomics Viewer. Cancer research. 2017;77(21):e31–e4. Epub 2017/11/03. doi: 10.1158/0008-5472.CAN-17-0337 29092934; PubMed Central PMCID: PMC5678989.

47. Feng J, Liu T, Qin B, Zhang Y, Liu XS. Identifying ChIP-seq enrichment using MACS. Nature protocols. 2012;7(9):1728–40. Epub 2012/09/01. doi: 10.1038/nprot.2012.101 22936215; PubMed Central PMCID: PMC3868217.

48. Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012;9(4):357–9. Epub 2012/03/06. doi: 10.1038/nmeth.1923 22388286; PubMed Central PMCID: PMC3322381.

49. Ramírez F, Dündar F, Diehl S, Grüning BA, Manke T. deepTools: a flexible platform for exploring deep-sequencing data. Nucleic Acids Res. 2014;42(Web Server issue):W187–91. Epub 2014/05/07. doi: 10.1093/nar/gku365 24799436; PubMed Central PMCID: PMC4086134.

Štítky
Genetika Reprodukční medicína

Článek vyšel v časopise

PLOS Genetics


2020 Číslo 6

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Kurzy Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

VIRTUÁLNÍ ČEKÁRNA ČR Jste praktický lékař nebo pediatr? Zapojte se! Jste praktik nebo pediatr? Zapojte se!

×