Abstract
Gen SMARCA1 koduje białko SNF2L, należące do rodziny ATPaz zależnych od chromatyny z podrodziny ISWI, które odgrywa kluczową w remodelowaniu chromatyny i regulacji ekspresji genów. W ostatnich latach rosnące zainteresowanie funkcją SMARCA1 zaowocowało licznymi badaniami, które wskazują na jego istotne znaczenie w rozwoju układu nerwowego, różnicowaniu komórek oraz utrzymaniu homeostazy epigenetycznej. Mutacje i zaburzenia regulacji SMARCA1 zostały powiązane z licznymi rodzajami nowotworów. W niniejszej pracy zebrano aktualny stan wiedzy na temat budowy, ekspresji, funkcji biologicznych oraz znaczenia klinicznego SMARCA1, wskazując na potencjalne zastosowanie tej wiedzy w dziedzinie onkologii.
References
1. Reyes AA, Marcum RD, He Y. Structure and Function of ATP-dependent Chromatin Remodeling Complexes. J Mol Biol. 2021 Jul 9;433(14):166929.
2. Han Y, Reyes AA, Malik S, He Y. Cryo-EM structure of SWI/SNF complex bound to a nucleosome. Nature. 2020 Mar;579(7799):452–5.
3. Clapier CR, Iwasa J, Cairns BR, Peterson CL. Mechanisms of action and regulation of ATP-dependent chromatin-remodelling complexes. Nat Rev Mol Cell Biol. 2017 Jul;18(7):407–22.
4. Quinn J, Fyrberg AM, Ganster RW, Schmidt MC, Peterson CL. DNA-binding properties of the yeast SWI/SNF complex. Nature. 1996 Feb;379(6568):844–7.
5. Mohrmann L, Verrijzer CP. Composition and functional specificity of SWI2/SNF2 class chromatin remodeling complexes. Biochim Biophys Acta BBA - Gene Struct Expr. 2005 Jan 11;1681(2):59–73.
6. Mashtalir N, D’Avino AR, Michel BC, Luo J, Pan J, Otto JE, et al. Modular Organization and Assembly of SWI/SNF Family Chromatin Remodeling Complexes. Cell. 2018 Nov 15;175(5):1272-1288.e20.
7. Liu X, Li M, Xia X, Li X, Chen Z. Mechanism of chromatin remodelling revealed by the Snf2-nucleosome structure. Nature. 2017 Apr;544(7651):440–5.
8. Clapier CR, Cairns BR. Regulation of ISWI involves inhibitory modules antagonized by nucleosomal epitopes. Nature. 2012 Dec;492(7428):280–4.
9. Goodwin LR, Picketts DJ. The role of ISWI chromatin remodeling complexes in brain development and neurodevelopmental disorders. Mol Cell Neurosci. 2018 Mar 1;87:55–64.
10. Xiao H, Sandaltzopoulos R, Wang HM, Hamiche A, Ranallo R, Lee KM, et al. Dual Functions of Largest NURF Subunit NURF301 in Nucleosome Sliding and Transcription Factor Interactions. Mol Cell. 2001 Sep 1;8(3):531–43.
11. Corona DFV, Längst G, Clapier CR, Bonte EJ, Ferrari S, Tamkun JW, et al. ISWI Is an ATP-Dependent Nucleosome Remodeling Factor. Mol Cell. 1999 Feb 1;3(2):239–45.
12. Kunert N, Brehm A. Novel Mi-2 related ATP-dependent chromatin remodelers. Epigenetics. 2009 May 16;4(4):209–11.
13. Ryan DP, Sundaramoorthy R, Martin D, Singh V, Owen‐Hughes T. The DNA‐binding domain of the Chd1 chromatin‐remodelling enzyme contains SANT and SLIDE domains. EMBO J. 2011 Jul 6;30(13):2596–609.
14. Konev AY, Tribus M, Park SY, Podhraski V, Lim CY, Emelyanov AV, et al. CHD1 Motor Protein Is Required for Deposition of Histone Variant H3.3 into Chromatin in Vivo. Science. 2007 Aug 24;317(5841):1087–90.
15. Li W, Mills AA. Architects of the genome: CHD dysfunction in cancer, developmental disorders and neurological syndromes. Epigenomics. 2014 Aug;6(4):381–95.
16. Ayala R, Willhoft O, Aramayo RJ, Wilkinson M, McCormack EA, Ocloo L, et al. Structure and regulation of the human INO80–nucleosome complex. Nature. 2018 Apr;556(7701):391–5.
17. Poli J, Gasser SM, Papamichos-Chronakis M. The INO80 remodeller in transcription, replication and repair. Philos Trans R Soc B Biol Sci. 2017 Aug 28;372(1731):20160290.
18. Goldberg AD, Banaszynski LA, Noh KM, Lewis PW, Elsaesser SJ, Stadler S, et al. Distinct Factors Control Histone Variant H3.3 Localization at Specific Genomic Regions. Cell. 2010 Mar 5;140(5):678–91.
19. PubChem. SMARCA1 - SNF2 related chromatin remodeling ATPase 1 (human) [Internet]. [cited 2025 Jan 30]. Available from: https://pubchem.ncbi.nlm.nih.gov/gene/SMARCA1/human
20. SMARCA1 - Probable global transcription activator SNF2L1 - Homo sapiens (Human) | UniProtKB | UniProt [Internet]. [cited 2025 Jan 30]. Available from: https://www.uniprot.org/uniprotkb/P28370/entry
21. Hota SK, Bhardwaj SK, Deindl S, Lin Y chi, Zhuang X, Bartholomew B. Nucleosome mobilization by ISW2 requires the concerted action of the ATPase and SLIDE domains. Nat Struct Mol Biol. 2013 Feb;20(2):222–9.
22. Euskirchen G, Auerbach RK, Snyder M. SWI/SNF Chromatin-remodeling Factors: Multiscale Analyses and Diverse Functions*. J Biol Chem. 2012 Sep 7;287(37):30897–905.
23. Barak O, Lazzaro MA, Cooch NS, Picketts DJ, Shiekhattar R. A Tissue-specific, Naturally Occurring Human SNF2L Variant Inactivates Chromatin Remodeling*. J Biol Chem. 2004 Oct 22;279(43):45130–8.
24. Toto M, D’Angelo G, Corona DFV. Regulation of ISWI chromatin remodelling activity. Chromosoma. 2014 Mar 1;123(1):91–102.
25. Sundaramoorthy R, Owen-Hughes T. Chromatin remodelling comes into focus. F1000Research. 2020 Aug 20;9:F1000 Faculty Rev-1011.
26. Zhang J, Gao Z, Yang Y, Li Z, Wu B, Fan C, et al. SNF2L maintains glutathione homeostasis by initiating SLC7A11 transcription through chromatin remodeling. Cell Death Dis. 2024 Nov 12;15(11):1–13.
27. Sjöstedt E, Zhong W, Fagerberg L, Karlsson M, Mitsios N, Adori C, et al. An atlas of the protein-coding genes in the human, pig, and mouse brain. Science. 2020 Mar 6;367(6482):eaay5947.
28. Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, et al. Proteomics. Tissue-based map of the human proteome. Science. 2015 Jan 23;347(6220):1260419.
29. Ye Y, Xiao Y, Wang W, Wang Q, Yearsley K, Wani AA, et al. Inhibition of Expression of the Chromatin Remodeling Gene, SNF2L, Selectively Leads to DNA Damage, Growth Inhibition, and Cancer Cell Death. Mol Cancer Res. 2009 Dec 16;7(12):1984–99.
30. Tsukiyama T, Becker PB, Wu C. ATP-dependent nucleosome disruption at a heat-shock promoter mediated by binding of GAGA transcription factor. Nature. 1994 Feb;367(6463):525–32.
31. Tsukiyama T, Daniel C, Tamkun J, Wu C. ISWI, a member of the SWl2/SNF2 ATPase family, encodes the 140 kDa subunit of the nucleosome remodeling factor. Cell. 1995 Dec 15;83(6):1021–6.
32. Barak O, Lazzaro MA, Lane WS, Speicher DW, Picketts DJ, Shiekhattar R. Isolation of human NURF: a regulator of Engrailed gene expression. EMBO J. 2003 Nov 17;22(22):6089–100.
33. Schwanbeck R, Xiao H, Wu C. Spatial Contacts and Nucleosome Step Movements Induced by the NURF Chromatin Remodeling Complex*. J Biol Chem. 2004 Sep 17;279(38):39933–41.
34. Kang J, Hamiche A, Wu C. GAL4 directs nucleosome sliding induced by NURF. EMBO J. 2002 Mar 15;21(6):1406–13.
35. Marques M, Laflamme L, Gervais AL, Gaudreau L. Reconciling the positive and negative roles of histone H2A.Z in gene transcription. Epigenetics. 2010 May 16;5(4):267–72.
36. Goldman JA, Garlick JD, Kingston RE. Chromatin Remodeling by Imitation Switch (ISWI) Class ATP-dependent Remodelers Is Stimulated by Histone Variant H2A.Z. J Biol Chem. 2010 Feb 12;285(7):4645–51.
37. Landry J, Sharov AA, Piao Y, Sharova LV, Xiao H, Southon E, et al. Essential Role of Chromatin Remodeling Protein Bptf in Early Mouse Embryos and Embryonic Stem Cells. PLOS Genet. 2008 Oct 31;4(10):e1000241.
38. Thompson PJ, Norton KA, Niri FH, Dawe CE, McDermid HE. CECR2 Is Involved in Spermatogenesis and Forms a Complex with SNF2H in the Testis. J Mol Biol. 2012 Feb 3;415(5):793–806.
39. Footz TK, Brinkman-Mills P, Banting GS, Maier SA, Riazi MA, Bridgland L, et al. Analysis of the Cat Eye Syndrome Critical Region in Humans and the Region of Conserved Synteny in Mice: A Search for Candidate Genes at or near the Human Chromosome 22 Pericentromere. Genome Res. 2001 Jun;11(6):1053–70.
40. Wu L, Zhao G, Xu S, Kuang J, Ming J, Wu G, et al. The nuclear factor CECR2 promotes somatic cell reprogramming by reorganizing the chromatin structure. J Biol Chem. 2021;296:100022.
41. Niri F, Terpstra AN, Lim KRQ, McDermid HE. Chromatin remodeling factor CECR2 forms tissue-specific complexes with CCAR2 and LUZP1. Biochem Cell Biol. 2021 Dec;99(6):759–65.
42. Phillips M, Cook ED, Marunde MR, Tonelli M, Khan L, Henrickson A, et al. The CECR2 bromodomain displays distinct binding modes to select for acetylated histone proteins versus non-histone ligands. BioRxiv Prepr Serv Biol. 2024 Dec 11;2024.12.09.627393.
43. Leduc RYM, Singh P, McDermid HE. Genetic backgrounds and modifier genes of NTD mouse models: An opportunity for greater understanding of the multifactorial etiology of neural tube defects. Birth Defects Res. 2017 Jan 30;109(2):140–52.
44. Norton KA, Niri F, Weatherill CB, Williams CE, Duong K, McDermid HE. Implantation failure and embryo loss contribute to subfertility in female mice mutant for chromatin remodeler Cecr2†. Biol Reprod. 2021 Apr 1;104(4):835–49.
45. Goodwin LR, Zapata G, Timpano S, Marenger J, Picketts DJ. Impaired SNF2L Chromatin Remodeling Prolongs Accessibility at Promoters Enriched for Fos/Jun Binding Sites and Delays Granule Neuron Differentiation. Front Mol Neurosci. 2021 Jul 6;14:680280.
46. Belgacem YH, Hamilton AM, Shim S, Spencer KA, Borodinsky LN. The Many Hats of Sonic Hedgehog Signaling in Nervous System Development and Disease. J Dev Biol. 2016 Dec;4(4):35.
47. Alvarez-Saavedra M, Lagali P, Yan K, Hashem E, Mears A, De Repentigny Y, et al. Coordinated epigenetic regulation of Engrailed-1 by the chromatin remodelers Smarca1 and Smarca5 mediates cerebellar morphogenesis. Epigenetics Chromatin. 2013 Apr 8;6(1):P105.
48. Aljabri AK, Hebron KE, Kriga Y, Caravaca JM, Althobaiti A, Emmons A, et al. Abstract LB_A23: The role of SMARCA1 in Rhabdomyosarcoma and skeletal muscle differentiation. Mol Cancer Ther. 2023 Dec 1;22(12_Supplement):LB_A23.
49. Ye Y, Xiao Y, Wang W, Wang Q, Yearsley K, Wani AA, et al. Inhibition of Expression of the Chromatin Remodeling Gene, SNF2L, Selectively Leads to DNA Damage, Growth Inhibition, and Cancer Cell Death. Mol Cancer Res. 2009 Dec 16;7(12):1984–99.
50. Dai L, Mugaanyi J, Zhang T, Tong J, Cai X, Lu C, et al. A pan-cancer bioinformatic analysis of the carcinogenic role of SMARCA1 in human carcinomas. PLoS ONE. 2022 Sep 20;17(9):e0274823.
51. Brown LK, Li G, Kanagasabai T, Chen Z. Abstract 2962: The oncogenic role of epigenetic factor, SNF2L in PCa. Cancer Res. 2022 Jun 15;82(12_Supplement):2962.
52. Li Y, Gong H, Wang P, Zhu Y, Peng H, Cui Y, et al. The emerging role of ISWI chromatin remodeling complexes in cancer. J Exp Clin Cancer Res. 2021 Nov 4;40(1):346.
53. Aydin ÖZ, Vermeulen W, Lans H. ISWI chromatin remodeling complexes in the DNA damage response. Cell Cycle Georget Tex. 2014;13(19):3016–25.
54. San Filippo J, Sung P, Klein H. Mechanism of eukaryotic homologous recombination. Annu Rev Biochem. 2008;77:229–57.
55. Nelligan A, Dungrawala H. SNF2L suppresses nascent DNA gap formation to promote DNA synthesis. Nucleic Acids Res. 2024 Nov 27;52(21):13003–18.
56. Finkel T. Signal transduction by reactive oxygen species. J Cell Biol. 2011 Jul 11;194(1):7–15.
57. He R, Liu Y, Fu W, He X, Liu S, Xiao D, et al. Mechanisms and cross-talk of regulated cell death and their epigenetic modifications in tumor progression. Mol Cancer. 2024 Nov 29;23(1):267.
58. Patil PA, Lombardo K, Sturtevant A, Mangray S, Yakirevich E. Loss of Expression of a Novel Chromatin Remodeler SMARCA1 in Soft Tissue Sarcoma. J Cytol Histol. 2018;9(6):524.
59. Fu C, Duan S, Zhang C, Cui X, Wang F, Wang L, et al. Identification of SMARCA1 as a key regulator for Colorectal Cancer [Internet]. bioRxiv; 2024 [cited 2025 Apr 28]. p. 2024.12.24.630213. Available from: https://www.biorxiv.org/content/10.1101/2024.12.24.630213v1
60. Ding L, Zhao Y, Dang S, Wang Y, Li X, Yu X, et al. Circular RNA circ-DONSON facilitates gastric cancer growth and invasion via NURF complex dependent activation of transcription factor SOX4. Mol Cancer. 2019 Mar 28;18(1):45.
61. Yip DJ, Corcoran CP, Alvarez-Saavedra M, DeMaria A, Rennick S, Mears AJ, et al. Snf2l regulates Foxg1-dependent progenitor cell expansion in the developing brain. Dev Cell. 2012 Apr 17;22(4):871–8.
62. Stopka T, Skoultchi AI. The ISWI ATPase Snf2h is required for early mouse development. Proc Natl Acad Sci. 2003 Nov 25;100(24):14097–102.
63. Li D, Wang X, Miao H, Liu H, Pang M, Guo H, et al. The lncRNA MIR99AHG directs alternative splicing of SMARCA1 by PTBP1 to enable invadopodia formation in colorectal cancer cells. Sci Signal. 2023 Sep 19;16(803):eadh4210.
64. Zhou J, Wang ,Dingxue, Tang ,Dongxin, and Huang W. Abnormal Activations of Super-Enhancers Enhance the Carcinogenicity in Lung Adenocarcinoma. Cancer Manag Res. 2020 Sep 15;12:8509–18.
65. Sun G, Wei Y, Zhou B, Wang M, Luan R, Bai Y, et al. BAP18 facilitates CTCF-mediated chromatin accessible to regulate enhancer activity in breast cancer. Cell Death Differ. 2023 May;30(5):1260–78.
66. Tang X, Chen W, Liu H, Liu N, Chen D, Tian D, et al. Research progress on SLC7A11 in the regulation of cystine/cysteine metabolism in tumors (Review). Oncol Lett. 2022 Feb 1;23(2):1–9.
67. Clapier CR, Cairns BR. The biology of chromatin remodeling complexes. Annu Rev Biochem. 2009;78:273–304.
68. Hota SK, Bruneau BG. ATP-dependent chromatin remodeling during mammalian development. Dev Camb Engl. 2016 Aug 15;143(16):2882–97.
69. Liu B, Yip RKH, Zhou Z. Chromatin Remodeling, DNA Damage Repair and Aging. Curr Genomics. 13(7):533–47.
This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License.
Copyright (c) 2025 Letters in Oncology Science