Structural insights into the human NuA4/TIP60 acetyltransferase and chromatin remodeling complex.
| Title: | Structural insights into the human NuA4/TIP60 acetyltransferase and chromatin remodeling complex. |
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| Authors: | Yang Z; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA, USA.; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA, USA.; Mameri A; St-Patrick Research Group in Basic Oncology, Oncology Division of the CHU de Québec-Université Laval Research Center, Laval University Cancer Research Center, Quebec City, QC, Canada.; Cattoglio C; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA, USA.; Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.; Lachance C; St-Patrick Research Group in Basic Oncology, Oncology Division of the CHU de Québec-Université Laval Research Center, Laval University Cancer Research Center, Quebec City, QC, Canada.; Florez Ariza AJ; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA, USA.; Biophysics Graduate Group, University of California, Berkeley, CA, USA.; Luo J; Institute for Systems Biology, Seattle, WA, USA.; Humbert J; St-Patrick Research Group in Basic Oncology, Oncology Division of the CHU de Québec-Université Laval Research Center, Laval University Cancer Research Center, Quebec City, QC, Canada.; Sudarshan D; St-Patrick Research Group in Basic Oncology, Oncology Division of the CHU de Québec-Université Laval Research Center, Laval University Cancer Research Center, Quebec City, QC, Canada.; Banerjea A; Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.; Galloy M; St-Patrick Research Group in Basic Oncology, Oncology Division of the CHU de Québec-Université Laval Research Center, Laval University Cancer Research Center, Quebec City, QC, Canada.; Fradet-Turcotte A; St-Patrick Research Group in Basic Oncology, Oncology Division of the CHU de Québec-Université Laval Research Center, Laval University Cancer Research Center, Quebec City, QC, Canada.; Lambert JP; Endocrinology Division of the CHU de Québec-Université Laval Research Center, Laval University Cancer Research Center, Quebec City, QC, Canada.; Ranish JA; Institute for Systems Biology, Seattle, WA, USA.; Côté J; St-Patrick Research Group in Basic Oncology, Oncology Division of the CHU de Québec-Université Laval Research Center, Laval University Cancer Research Center, Quebec City, QC, Canada.; Nogales E; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA, USA.; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA, USA.; Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.; Molecular Biophysics and Integrative Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA. |
| Source: | Science (New York, N.Y.) [Science] 2024 Aug 23; Vol. 385 (6711), pp. eadl5816. Date of Electronic Publication: 2024 Aug 23. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
| Language: | English |
| Journal Info: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE |
| Imprint Name(s): | Publication: : Washington, DC : American Association for the Advancement of Science; Original Publication: New York, N.Y. : [s.n.] 1880- |
| MeSH Terms: | Lysine Acetyltransferase 5*/chemistry ; Chromatin Assembly and Disassembly*; DNA-Binding Proteins/chemistry ; Histones/chemistry ; Nuclear Proteins/chemistry ; Nucleosomes/chemistry ; Nucleosomes/ultrastructure ; Transcription Factors/chemistry ; Humans ; Acetylation ; Adaptor Proteins, Signal Transducing ; Cryoelectron Microscopy ; Protein Domains |
| Abstract: | The human nucleosome acetyltransferase of histone H4 (NuA4)/Tat-interactive protein, 60 kilodalton (TIP60) coactivator complex, a fusion of the yeast switch/sucrose nonfermentable related 1 (SWR1) and NuA4 complexes, both incorporates the histone variant H2A.Z into nucleosomes and acetylates histones H4, H2A, and H2A.Z to regulate gene expression and maintain genome stability. Our cryo-electron microscopy studies show that, within the NuA4/TIP60 complex, the E1A binding protein P400 (EP400) subunit serves as a scaffold holding the different functional modules in specific positions, creating a distinct arrangement of the actin-related protein (ARP) module. EP400 interacts with the transformation/transcription domain-associated protein (TRRAP) subunit by using a footprint that overlaps with that of the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex, preventing the formation of a hybrid complex. Loss of the TRRAP subunit leads to mislocalization of NuA4/TIP60, resulting in the redistribution of H2A.Z and its acetylation across the genome, emphasizing the dual functionality of NuA4/TIP60 as a single macromolecular assembly. |
| References: | Science. 2018 Oct 12;362(6411):. (PMID: 30309918); Sci Adv. 2022 Dec 9;8(49):eadd3189. (PMID: 36490333); Epigenetics Chromatin. 2019 Jun 14;12(1):37. (PMID: 31200754); Elife. 2022 Oct 20;11:. (PMID: 36263929); Nature. 2016 Feb 4;530(7588):113-6. (PMID: 26814966); Cell Discov. 2024 Feb 8;10(1):15. (PMID: 38331872); Nat Struct Mol Biol. 2011 Nov 13;18(12):1358-65. (PMID: 22081016); Cell Discov. 2022 Nov 22;8(1):125. (PMID: 36414614); Nucleic Acids Res. 2018 Sep 19;46(16):8197-8215. (PMID: 29986055); Cell. 2001 Aug 10;106(3):297-307. (PMID: 11509179); Front Cell Dev Biol. 2021 Sep 16;9:729338. (PMID: 34604228); Genes Dev. 2018 Jan 1;32(1):58-69. (PMID: 29437725); Nucleic Acids Res. 2016 Jul 8;44(W1):W160-5. (PMID: 27079975); Curr Opin Struct Biol. 2020 Apr;61:50-58. (PMID: 31838293); Mol Cell. 2016 May 5;62(3):409-421. (PMID: 27153538); J Comput Chem. 2004 Oct;25(13):1605-12. (PMID: 15264254); Bioinformatics. 2012 Jul 15;28(14):1919-20. (PMID: 22576172); J Struct Biol. 2015 Nov;192(2):216-21. (PMID: 26278980); Nat Methods. 2017 Mar;14(3):290-296. (PMID: 28165473); Nat Commun. 2019 May 29;10(1):2361. (PMID: 31142747); Mol Cell. 2022 Dec 15;82(24):4627-4646.e14. (PMID: 36417913); Mol Cell Biol. 2018 Apr 16;38(9):. (PMID: 29463645); Nat Struct Mol Biol. 2016 Apr;23(4):309-16. (PMID: 26974126); Mol Cell. 2015 Sep 3;59(5):794-806. (PMID: 26340423); Nature. 2023 Feb;614(7949):732-741. (PMID: 36792830); Genes Dev. 2006 Mar 15;20(6):700-10. (PMID: 16543222); Genes Dev. 2009 Jul 1;23(13):1522-33. (PMID: 19515975); Cell. 2013 Sep 12;154(6):1232-45. (PMID: 24034247); Nat Methods. 2022 Jun;19(6):679-682. (PMID: 35637307); Genome Biol. 2014;15(12):550. (PMID: 25516281); Genes Dev. 2001 Jul 1;15(13):1619-24. (PMID: 11445536); Methods Enzymol. 2016;573:303-18. (PMID: 27372759); Nature. 2022 Oct;610(7932):569-574. (PMID: 36198799); DNA Repair (Amst). 2022 May;113:103315. (PMID: 35278769); Nucleic Acids Res. 2017 Jul 7;45(12):7249-7260. (PMID: 28499038); Am J Hum Genet. 2020 Sep 3;107(3):564-574. (PMID: 32822602); Nat Struct Mol Biol. 2023 Sep;30(9):1337-1345. (PMID: 37550452); Mol Cell. 2016 Jan 7;61(1):27-38. (PMID: 26669263); Cell Rep. 2015 Oct 20;13(3):621-633. (PMID: 26456817); Nat Struct Mol Biol. 2016 Apr;23(4):317-23. (PMID: 26974124); Curr Opin Genet Dev. 2004 Apr;14(2):147-54. (PMID: 15196461); J Cell Biol. 2010 Oct 4;191(1):31-43. (PMID: 20876283); Acta Crystallogr D Struct Biol. 2018 Jun 1;74(Pt 6):531-544. (PMID: 29872004); Nat Methods. 2017 Jun;14(6):615-620. (PMID: 28417998); Trends Biochem Sci. 2022 Nov;47(11):909-920. (PMID: 35606214); Gigascience. 2021 Feb 16;10(2):. (PMID: 33590861); Mol Cell Proteomics. 2022 Jul;21(7):100253. (PMID: 35636729); Nat Genet. 1999 Feb;21(2):220-4. (PMID: 9988278); Nature. 2021 Aug;596(7873):583-589. (PMID: 34265844); Clin Breast Cancer. 2023 Feb;23(2):125-134. (PMID: 36463002); Mol Cell Biol. 2002 Aug;22(16):5650-61. (PMID: 12138177); Epigenetics Chromatin. 2015 Nov 06;8:45. (PMID: 26550034); Cancer Sci. 2023 Jun;114(6):2400-2413. (PMID: 36916958); Nat Chem Biol. 2018 May;14(5):431-441. (PMID: 29581585); Biochem Soc Trans. 2019 Dec 20;47(6):1597-1608. (PMID: 31769470); Trends Cell Biol. 2006 Sep;16(9):433-42. (PMID: 16904321); Proc Natl Acad Sci U S A. 2015 Oct 13;112(41):E5600-7. (PMID: 26401017); Nat Commun. 2019 Apr 23;10(1):1827. (PMID: 31015444); Cell Death Dis. 2022 Jul 20;13(7):627. (PMID: 35853868); Genome Biol. 2008;9(9):R137. (PMID: 18798982); Nat Methods. 2012 Mar 04;9(4):357-9. (PMID: 22388286); Genome Res. 2002 Jun;12(6):996-1006. (PMID: 12045153); Nat Struct Mol Biol. 2021 Dec;28(12):989-996. (PMID: 34811519); Nat Struct Mol Biol. 2005 Dec;12(12):1064-71. (PMID: 16299513); Transl Psychiatry. 2021 Feb 18;11(1):132. (PMID: 33602898); Cell. 1998 Aug 7;94(3):363-74. (PMID: 9708738); J Struct Biol. 2005 Oct;152(1):36-51. (PMID: 16182563); Nat Commun. 2018 Mar 20;9(1):1147. (PMID: 29559617); Cell Death Differ. 2016 Jul;23(7):1198-208. (PMID: 26915295); Nucleic Acids Res. 2020 Jan 8;48(D1):D58-D64. (PMID: 31740966); Cell Res. 2018 Nov;28(11):1121-1123. (PMID: 30337683); Bioinformatics. 2013 Jan 1;29(1):15-21. (PMID: 23104886); Genes Dev. 2007 Aug 1;21(15):1869-81. (PMID: 17671089); Protein Sci. 2020 Apr;29(4):1069-1078. (PMID: 31730249); Cell. 2008 Jul 11;134(1):162-74. (PMID: 18614019); Bioinformatics. 2022 May 13;38(10):2943-2945. (PMID: 35561197); Biochem J. 2021 Dec 22;478(24):4169-4185. (PMID: 34783343); EMBO Rep. 2003 Jun;4(6):575-80. (PMID: 12776177); Biochemistry. 2006 May 2;45(17):5671-7. (PMID: 16634648); Nat Genet. 2013 Oct;45(10):1113-20. (PMID: 24071849); Nat Biotechnol. 2011 Jan;29(1):24-6. (PMID: 21221095); Science. 2012 Apr 27;336(6080):477-81. (PMID: 22539723); Oncogene. 2013 Sep 5;32(36):4243-51. (PMID: 23108396); Cell. 2010 Oct 15;143(2):313-24. (PMID: 20946988); Nat Methods. 2012 Sep;9(9):904-6. (PMID: 22772728); Nat Commun. 2018 Aug 17;9(1):3309. (PMID: 30120252); Int J Mol Sci. 2021 Jan 12;22(2):. (PMID: 33445503); Cell. 2019 Sep 5;178(6):1421-1436.e24. (PMID: 31491386); Biochim Biophys Acta. 2013 Mar-Apr;1819(3-4):290-302. (PMID: 24459731); Genes Dev. 2022 Jun 1;36(11-12):664-683. (PMID: 35710139); Cell Rep. 2016 Jun 28;16(1):37-47. (PMID: 27320910); Commun Biol. 2019 Jun 19;2:218. (PMID: 31240256); Cell. 2017 Jul 27;170(3):564-576.e16. (PMID: 28753430); Nat Methods. 2017 Apr;14(4):331-332. (PMID: 28250466); Genes Dev. 2022 Mar 1;36(5-6):313-330. (PMID: 35210222); Cell. 2013 Sep 12;154(6):1220-31. (PMID: 24034246); Nat Struct Mol Biol. 2018 Jan;25(1):37-44. (PMID: 29323271); Nucleic Acids Res. 2022 Jul 5;50(W1):W345-W351. (PMID: 35446428); Blood. 2020 Oct 8;136(15):1735-1747. (PMID: 32542325); Elife. 2019 Dec 30;8:. (PMID: 31886770); Mol Cell Biol. 2008 Apr;28(7):2257-70. (PMID: 18212047); Nucleic Acids Res. 2003 Jul 1;31(13):3320-3. (PMID: 12824317); Nucleic Acids Res. 2019 Jul 9;47(12):6208-6224. (PMID: 31081019); J Biol Chem. 2010 May 21;285(21):15966-77. (PMID: 20332092); Int J Cancer. 2016 Mar 1;138(5):1067-75. (PMID: 26096807); Nature. 2007 Aug 30;448(7157):1063-7. (PMID: 17728759); Front Cell Dev Biol. 2023 Apr 07;11:1134268. (PMID: 37091973); Curr Opin Cell Biol. 2021 Jun;70:1-9. (PMID: 33217681); Bioinformatics. 2010 Mar 15;26(6):841-2. (PMID: 20110278); J Biol Chem. 2012 Mar 2;287(10):7780-91. (PMID: 22249179); Nature. 2018 Apr;556(7701):386-390. (PMID: 29643509); Am J Hum Genet. 2019 May 2;104(5):815-834. (PMID: 31031012); J Cell Biol. 2012 Dec 24;199(7):1067-81. (PMID: 23266955); Proc Natl Acad Sci U S A. 2022 Nov 29;119(48):e2214313119. (PMID: 36417436); Nature. 2023 Jan;613(7942):195-202. (PMID: 36544023); Cell. 2023 Nov 22;186(24):5290-5307.e26. (PMID: 37922899); Oncogene. 2007 Aug 13;26(37):5358-72. (PMID: 17694078); Cell Stem Cell. 2023 Nov 2;30(11):1503-1519.e8. (PMID: 37863054); J Mol Cell Biol. 2019 May 1;11(5):345-355. (PMID: 30388237) |
| Grant Information: | United States HHMI Howard Hughes Medical Institute; R01 GM136974 United States GM NIGMS NIH HHS; R35 GM127018 United States GM NIGMS NIH HHS |
| Substance Nomenclature: | 0 (Adaptor Proteins, Signal Transducing); 0 (DNA-Binding Proteins); 0 (Histones); EC 2.3.1.48 (KAT5 protein, human); EC 2.3.1.48 (Lysine Acetyltransferase 5); 0 (Nuclear Proteins); 0 (Nucleosomes); 0 (Transcription Factors); 0 (transformation-transcription domain-associated protein) |
| Entry Date(s): | Date Created: 20240801 Date Completed: 20240822 Latest Revision: 20250530 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11995519 |
| DOI: | 10.1126/science.adl5816 |
| PMID: | 39088653 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural