Transcriptional activation domains interact with ATPase subunits of yeast chromatin remodelling complexes SWI/SNF, RSC and INO80.


Journal

Current genetics
ISSN: 1432-0983
Titre abrégé: Curr Genet
Pays: United States
ID NLM: 8004904

Informations de publication

Date de publication:
05 Sep 2024
Historique:
received: 11 06 2024
accepted: 07 08 2024
revised: 25 07 2024
medline: 5 9 2024
pubmed: 5 9 2024
entrez: 5 9 2024
Statut: epublish

Résumé

Chromatin remodelling complexes (CRC) are ATP-dependent molecular machines important for the dynamic organization of nucleosomes along eukaryotic DNA. CRCs SWI/SNF, RSC and INO80 can move positioned nucleosomes in promoter DNA, leading to nucleosome-depleted regions which facilitate access of general transcription factors. This function is strongly supported by transcriptional activators being able to interact with subunits of various CRCs. In this work we show that SWI/SNF subunits Swi1, Swi2, Snf5 and Snf6 can bind to activation domains of Ino2 required for expression of phospholipid biosynthetic genes in yeast. We identify an activator binding domain (ABD) of ATPase Swi2 and show that this ABD is functionally dispensable, presumably because ABDs of other SWI/SNF subunits can compensate for the loss. In contrast, mutational characterization of the ABD of the Swi2-related ATPase Sth1 revealed that some conserved basic and hydrophobic amino acids within this domain are essential for the function of Sth1. While ABDs of Swi2 and Sth1 define separate functional protein domains, mapping of an ABD within ATPase Ino80 showed co-localization with its HSA domain also required for binding actin-related proteins. Comparative interaction studies finally demonstrated that several unrelated activators each exhibit a specific binding pattern with ABDs of Swi2, Sth1 and Ino80.

Identifiants

pubmed: 39235627
doi: 10.1007/s00294-024-01300-x
pii: 10.1007/s00294-024-01300-x
doi:

Substances chimiques

Saccharomyces cerevisiae Proteins 0
Adenosine Triphosphatases EC 3.6.1.-
Transcription Factors 0
DNA-Binding Proteins 0
INO80 complex, S cerevisiae 0
Chromosomal Proteins, Non-Histone 0
RSC complex, S cerevisiae 0
STH1 protein, S cerevisiae EC 3.6.1.-
INO2 protein, S cerevisiae 0
SNF2 protein, S cerevisiae EC 3.6.1.-
SWI1 protein, S cerevisiae 0
Nuclear Proteins 0
Cell Cycle Proteins 0
Basic Helix-Loop-Helix Transcription Factors 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

15

Informations de copyright

© 2024. The Author(s).

Références

Bakshi R, Prakash T, Dash D, Brahmachari V (2004) In silico characterization of the INO80 subfamily of SWI2/SNF2 chromatin remodeling proteins. Biochem Biophys Res Commun 320:197–204. https://doi.org/10.1016/j.bbrc.2004.05.147
doi: 10.1016/j.bbrc.2004.05.147 pubmed: 15207721
Bakshi R, Mehta AK, Sharma R, Maiti S, Pasha S, Brahmachari V (2006) Characterization of a human SWI2/SNF2 like protein hINO80: demonstration of catalytic and DNA binding activity. Biochem Biophys Res Commun 339:313–320. https://doi.org/10.1016/j.bbrc.2005.10.206
doi: 10.1016/j.bbrc.2005.10.206 pubmed: 16298340
Bao Y, Shen X (2007) INO80 subfamily of chromatin remodeling complexes. Mutat Res 618:18–29. https://doi.org/10.1016/j.mrfmmm.2006.10.006
doi: 10.1016/j.mrfmmm.2006.10.006 pubmed: 17316710 pmcid: 2699258
Biegel JA, Busse TM, Weissman BE (2014) SWI/SNF chromatin remodeling complexes and cancer. Am J Med Genet 166C:350–366. https://doi.org/10.1002/ajmg.c.31410
doi: 10.1002/ajmg.c.31410 pubmed: 25169151
Brahma S, Ngubo M, Paul S, Udugama M, Bartholomew B (2018) The Arp8 and Arp4 module acts as a DNA sensor controlling INO80 chromatin remodeling. Nat Commun 9:3309. https://doi.org/10.1038/s41467-018-05710-7
doi: 10.1038/s41467-018-05710-7 pubmed: 30120252 pmcid: 6098158
Cairns BR, Lorch Y, Li Y, Zhang M, Lacomis L, Erdjument-Bromage H, Tempst P, Du J, Laurent B, Kornberg RD (1996) RSC, an essential, abundant chromatin-remodeling complex. Cell 87:1249–1260. https://doi.org/10.1016/s0092-8674(00)81820-6
doi: 10.1016/s0092-8674(00)81820-6 pubmed: 8980231
Chou KY, Lee JY, Kim KB, Kim E, Lee HS, Ryu HY (2023) Histone modification in Saccharomyces cerevisiae: a review of the current status. Comput Struct Biotechnol J 21:1843–1850. https://doi.org/10.1016/j.csbj.2023.02.037
doi: 10.1016/j.csbj.2023.02.037 pubmed: 36915383 pmcid: 10006725
Clapier CR, Iwasa J, Cairns BR, Peterson CL (2017) Mechanisms of action and regulation of ATP-dependent chromatin-remodelling complexes. Nat Rev Mol Cell Biol 18:407–422. https://doi.org/10.1038/nrm.2017.26
doi: 10.1038/nrm.2017.26 pubmed: 28512350 pmcid: 8127953
Cosma MP, Tanaka T, Nasmyth K (1999) Ordered recruitment of transcription and chromatin remodeling factors to a cell cycle- and developmentally regulated promoter. Cell 97:299–311. https://doi.org/10.1016/s0092-8674(00)80740-0
doi: 10.1016/s0092-8674(00)80740-0 pubmed: 10319811
Dietz M, Heyken WT, Hoppen J, Geburtig S, Schüller HJ (2003) TFIIB and subunits of the SAGA complex are involved in transcriptional activation of phospholipid biosynthetic genes by the regulatory protein Ino2 in the yeast Saccharomyces cerevisiae. Mol Microbiol 48:1119–1130. https://doi.org/10.1046/j.1365-2958.2003.03501.x
doi: 10.1046/j.1365-2958.2003.03501.x pubmed: 12753200
Ebbert R, Birkmann A, Schüller HJ (1999) The product of the SNF2/SWI2 paralogue INO80 of Saccharomyces cerevisiae required for efficient expression of various yeast structural genes is part of a high-molecular-weight protein complex. Mol Microbiol 32:741–751. https://doi.org/10.1046/j.1365-2958.1999.01390.x
doi: 10.1046/j.1365-2958.1999.01390.x pubmed: 10361278
Engelhardt M, Hintze S, Wendegatz EC, Lettow J, Schüller HJ (2023) Ino2, activator of yeast phospholipid biosynthetic genes, interacts with basal transcription factors TFIIA and Bdf1. Curr Genet 69:289–300. https://doi.org/10.1007/s00294-023-01277-z
doi: 10.1007/s00294-023-01277-z pubmed: 37947853 pmcid: 10716077
Erijman A, Kozlowski L, Sohrabi-Jahromi S, Fishburn J, Warfield L, Schreiber J, Noble WS, Söding J, Hahn S (2020) A high-throughput screen for transcription activation domains reveals their sequence features and permits prediction by deep learning. Mol Cell 78:890–902. https://doi.org/10.1016/j.molcel.2020.04.020
doi: 10.1016/j.molcel.2020.04.020 pubmed: 32416068 pmcid: 7275923
Eustermann S, Patel AB, Hopfner KP, He Y, Korber P (2024) Energy-driven genome regulation by ATP-dependent chromatin remodellers. Nat Rev Mol Cell Biol 25:309–332. https://doi.org/10.1038/s41580-023-00683-y
doi: 10.1038/s41580-023-00683-y pubmed: 38081975
Ford J, Odeyale O, Eskandar A, Kouba N, Shen CH (2007) A SWI/SNF- and INO80-dependent nucleosome movement at the INO1 promoter. Biochem Biophys Res Commun 361:974–979. https://doi.org/10.1016/j.bbrc.2007.07.109
doi: 10.1016/j.bbrc.2007.07.109 pubmed: 17681272 pmcid: 2034749
Ford J, Odeyale O, Shen CH (2008) Activator-dependent recruitment of SWI/SNF and INO80 during INO1 activation. Biochem Biophys Res Commun 373:602–606. https://doi.org/10.1016/j.bbrc.2008.06.079
doi: 10.1016/j.bbrc.2008.06.079 pubmed: 18593569 pmcid: 2536487
Gietz RD, Sugino A (1988) New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sites. Gene 74:527–534. https://doi.org/10.1016/0378-1119(88)90185-0
doi: 10.1016/0378-1119(88)90185-0 pubmed: 3073106
Hahn S (2018) Phase separation, protein disorder, and enhancer function. Cell 175:1723–1725. https://doi.org/10.1016/j.cell.2018.11.034
doi: 10.1016/j.cell.2018.11.034 pubmed: 30550782
Han Y, Reyes AA, Malik S, He Y (2020) Cryo-EM structure of SWI/SNF complex bound to a nucleosome. Nature 579:452–455. https://doi.org/10.1038/s41586-020-2087-1
doi: 10.1038/s41586-020-2087-1 pubmed: 32188938 pmcid: 7319049
Hartley PD, Madhani HD (2009) Mechanisms that specify promoter nucleosome location and identity. Cell 137:445–458. https://doi.org/10.1016/j.cell.2009.02.043
doi: 10.1016/j.cell.2009.02.043 pubmed: 19410542 pmcid: 2677553
Hassan AH, Awad S, Al-Natour Z, Othman S, Mustafa F, Rizvi TA (2007) Selective recognition of acetylated histones by bromodomains in transcriptional co-activators. Biochem J 402:125–133. https://doi.org/10.1042/BJ20060907
doi: 10.1042/BJ20060907 pubmed: 17049045 pmcid: 1783998
Hintze S, Engelhardt M, van Diepen L, Witt E, Schüller HJ (2017) Multiple Taf subunits of TFIID interact with Ino2 activation domains and contribute to expression of genes required for yeast phospholipid biosynthesis. Mol Microbiol 106:876–890. https://doi.org/10.1111/mmi.13850
doi: 10.1111/mmi.13850 pubmed: 28994223
Hsieh LJ, Gourdet MA, Moore CM, Muñoz EN, Gamarra N, Ramani V, Narlikar GJ (2022) A hexasome is the preferred substrate for the INO80 chromatin remodeling complex, allowing versatility of function. Mol Cell 82:2098–2112. https://doi.org/10.1016/j.molcel.2022.04.026
doi: 10.1016/j.molcel.2022.04.026 pubmed: 35597239 pmcid: 9351570
Hu Z, Chen K, Li W, Tyler JK (2014) A matter of access. Nucleosome disassembly from gene promoters is the central goal of transcriptional activators. Transcription 5:e29355. https://doi.org/10.4161/trns.29355
doi: 10.4161/trns.29355 pubmed: 25764221 pmcid: 4215176
Imai Y, Matsushima Y, Sugimura T, Terada M (1991) A simple and rapid method for generating a deletion by PCR. Nucleic Acids Res 19:2785. https://doi.org/10.1093/nar/19.10.2785
doi: 10.1093/nar/19.10.2785 pubmed: 1645866 pmcid: 328208
Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O, Tunyasuvunakool K, Bates R, Žídek A, Potapenko A, Bridgland A, Meyer C, Kohl SAA, Ballard AJ, Cowie A, Romera-Paredes B, Nikolov S, Jain R, Adler J, Back T, Petersen S, Reiman D, Clancy E, Zielinski M, Steinegger M, Pacholska M, Berghammer T, Bodenstein S, Silver D, Vinyals O, Senior AW, Kavukcuoglu K, Kohli P, Hassabis D (2021) Highly accurate protein structure prediction with AlphaFold. Nature 596:583–589. https://doi.org/10.1038/s41586-021-03819-2
doi: 10.1038/s41586-021-03819-2 pubmed: 34265844 pmcid: 8371605
Kadosh D, Struhl K (1997) Repression by Ume6 involves recruitment of a complex containing Sin3 corepressor and Rpd3 histone deacetylase to target promoters. Cell 89:365–371. https://doi.org/10.1016/s0092-8674(00)80217-2
doi: 10.1016/s0092-8674(00)80217-2 pubmed: 9150136
Kalpana GV, Marmon S, Wang W, Crabtree GR, Goff SP (1994) Binding and stimulation of HIV-1 integrase by a human homolog of yeast transcription factor SNF5. Science 266:2002–2006. https://doi.org/10.1126/science.7801128
doi: 10.1126/science.7801128 pubmed: 7801128
Kim JH, Saraf A, Florens L, Washburn M, Workman JL (2010) Gcn5 regulates the dissociation of SWI/SNF from chromatin by acetylation of Swi2/Snf2. Genes Dev 24:2766–2771. https://doi.org/10.1101/gad.1979710
doi: 10.1101/gad.1979710 pubmed: 21159817 pmcid: 3003194
Knoll KR, Eustermann S, Niebauer V, Oberbeckmann E, Stoehr G, Schall K, Tosi A, Schwarz M, Buchfellner A, Korber P, Hopfner KP (2018) The nuclear actin-containing Arp8 module is a linker DNA sensor driving INO80 chromatin remodeling. Nat Struct Mol Biol 25:823–832. https://doi.org/10.1038/s41594-018-0115-8
doi: 10.1038/s41594-018-0115-8 pubmed: 30177756
Kunert F, Metzner FJ, Jung J, Höpfler M, Woike S, Schall K, Kostrewa D, Moldt M, Chen JX, Bantele S, Pfander B, Eustermann S, Hopfner KP (2022) Structural mechanism of extranucleosomal DNA readout by the INO80 complex. Sci Adv 8:eadd3189. https://doi.org/10.1126/sciadv.add3189
doi: 10.1126/sciadv.add3189 pubmed: 36490333 pmcid: 9733932
Lorch Y, Kornberg RD (2017) Chromatin-remodeling for transcription. Q Rev Biophys 50:e5. https://doi.org/10.1017/S003358351700004X
doi: 10.1017/S003358351700004X pubmed: 29233217
Malik S, Roeder RG (2023) Regulation of the RNA polymerase II pre-initiation complex by its associated coactivators. Nat Rev Genet 24:767–782. https://doi.org/10.1038/s41576-023-00630-9
doi: 10.1038/s41576-023-00630-9 pubmed: 37532915
Mittal C, Lang O, Lai WKM, Pugh BF (2022) An integrated SAGA and TFIID PIC assembly pathway selective for poised and induced promoters. Genes Dev 36:985–1001. https://doi.org/10.1101/gad.350026.122
doi: 10.1101/gad.350026.122 pubmed: 36302553 pmcid: 9732905
Mumberg D, Müller R, Funk M (1994) Regulatable promoters of Saccharomyces cerevisiae: comparison of transcriptional activity and their use for heterologous expression. Nucleic Acids Res 22:5767–5768. https://doi.org/10.1093/nar/22.25.5767
doi: 10.1093/nar/22.25.5767 pubmed: 7838736 pmcid: 310147
Neely KE, Hassan AH, Wallberg AE, Steger DJ, Cairns BR, Wright AP, Workman JL (1999) Activation domain-mediated targeting of the SWI/SNF complex to promoters stimulates transcription from nucleosome arrays. Mol Cell 4:649–655. https://doi.org/10.1016/s1097-2765(00)80216-6
doi: 10.1016/s1097-2765(00)80216-6 pubmed: 10549297
Neely KE, Hassan AH, Brown CE, Howe L, Workman JL (2002) Transcription activator interactions with multiple SWI/SNF subunits. Mol Cell Biol 22:1615–1625. https://doi.org/10.1128/MCB.22.6.1615-1625.2002
doi: 10.1128/MCB.22.6.1615-1625.2002 pubmed: 11865042 pmcid: 135607
Neigeborn L, Carlson M (1984) Genes affecting the regulation of SUC2 gene expression by glucose repression in Saccharomyces cerevisiae. Genetics 108:845–858. https://doi.org/10.1093/genetics/108.4.845
doi: 10.1093/genetics/108.4.845 pubmed: 6392017 pmcid: 1224269
Papamichos-Chronakis M, Watanabe S, Rando OJ, Peterson CL (2011) Global regulation of H2A.Z localization by the INO80 chromatin-remodeling enzyme is essential for genome integrity. Cell 144:200–213. https://doi.org/10.1016/j.cell.2010.12.021
doi: 10.1016/j.cell.2010.12.021 pubmed: 21241891 pmcid: 3035940
Patel AB, Moore CM, Greber BJ, Luo J, Zukin SA, Ranish J, Nogales E (2019) Architecture of the chromatin remodeler RSC and insights into its nucleosome engagement. Elife 8:e54449. https://doi.org/10.7554/eLife.54449
doi: 10.7554/eLife.54449 pubmed: 31886770 pmcid: 6959994
Peterson CL, Herskowitz I (1992) Characterization of the yeast SWI1, SWI2, and SWI3 genes, which encode a global activator of transcription. Cell 68:573–583. https://doi.org/10.1016/0092-8674(92)90192-f
doi: 10.1016/0092-8674(92)90192-f pubmed: 1339306
Peterson CL, Kruger W, Herskowitz I (1991) A functional interaction between the C-terminal domain of RNA polymerase II and the negative regulator SIN1. Cell 64:1135–1143. https://doi.org/10.1016/0092-8674(91)90268-4
doi: 10.1016/0092-8674(91)90268-4 pubmed: 2004420
Prochasson P, Neely KE, Hassan AH, Li B, Workman JL (2003) Targeting activity is required for SWI/SNF function in vivo and is accomplished through two partially redundant activator-interaction domains. Mol Cell 12:983–990. https://doi.org/10.1016/s1097-2765(03)00366-6
doi: 10.1016/s1097-2765(03)00366-6 pubmed: 14580348
Schwank S, Ebbert R, Rautenstrauss K, Schweizer E, Schüller HJ (1995) Yeast transcriptional activator INO2 interacts as an Ino2p/Ino4p basic helix-loop-helix heteromeric complex with the inositol/choline-responsive element necessary for expression of phospholipid biosynthetic genes in Saccharomyces cerevisiae. Nucleic Acids Res 23:230–237. https://doi.org/10.1093/nar/23.2.230
doi: 10.1093/nar/23.2.230 pubmed: 7862526 pmcid: 306659
Sen P, Ghosh S, Pugh BF, Bartholomew B (2011) A new, highly conserved domain in Swi2/Snf2 is required for SWI/SNF remodeling. Nucleic Acids Res 39:9155–9166. https://doi.org/10.1093/nar/gkr622
doi: 10.1093/nar/gkr622 pubmed: 21835776 pmcid: 3241646
Shen X, Mizuguchi G, Hamiche A, Wu C (2000) A chromatin remodelling complex involved in transcription and DNA processing. Nature 406:541–544. https://doi.org/10.1038/35020123
doi: 10.1038/35020123 pubmed: 10952318
Shen X, Ranallo R, Choi E, Wu C (2003) Involvement of actin-related proteins in ATP-dependent chromatin remodeling. Mol Cell 12:147–155. https://doi.org/10.1016/s1097-2765(03)00264-8
doi: 10.1016/s1097-2765(03)00264-8 pubmed: 12887900
Sikorski RS, Boeke JD (1991) In vitro mutagenesis and plasmid shuffling: from cloned gene to mutant yeast. Methods Enzymol 194:302–318. https://doi.org/10.1016/0076-6879(91)94023-6
doi: 10.1016/0076-6879(91)94023-6 pubmed: 2005795
Stern M, Jensen R, Herskowitz I (1984) Five SWI genes are required for expression of the HO gene in yeast. J Mol Biol 178:853–868. https://doi.org/10.1016/0022-2836(84)90315-2
doi: 10.1016/0022-2836(84)90315-2 pubmed: 6436497
Sudarsanam P, Iyer VR, Brown PO, Winston F (2000) Whole-genome expression analysis of snf/swi mutants of Saccharomyces cerevisiae. Proc Natl Acad Sci USA 97:3364–3369. https://doi.org/10.1073/pnas.97.7.3364
doi: 10.1073/pnas.97.7.3364 pubmed: 10725359 pmcid: 16245
Szerlong H, Hinata K, Viswanathan R, Erdjument-Bromage H, Tempst P, Cairns BR (2008) The HSA domain binds nuclear actin-related proteins to regulate chromatin-remodeling ATPases. Nat Struct Mol Biol 15:469–476. https://doi.org/10.1038/nsmb.1403
doi: 10.1038/nsmb.1403 pubmed: 18408732 pmcid: 2810487
Wagner FR, Dienemann C, Wang H, Stützer A, Tegunov D, Urlaub H, Cramer P (2020) Structure of SWI/SNF chromatin remodeller RSC bound to a nucleosome. Nature 579:448–451. https://doi.org/10.1038/s41586-020-2088-0
doi: 10.1038/s41586-020-2088-0 pubmed: 32188943 pmcid: 7093204
Wang T, Zhang J, Zhang X, Tu X (2012) Solution structure of SWI1 AT-rich interaction domain from Saccharomyces cerevisiae and its nonspecific binding to DNA. Proteins 80:1911–1917. https://doi.org/10.1002/prot.24091
doi: 10.1002/prot.24091 pubmed: 22488857
Wang C, Guo Z, Zhan X, Yang F, Wu M, Zhang X (2020) Structure of the yeast Swi/Snf complex in a nucleosome free state. Nat Commun 11:3398. https://doi.org/10.1038/s41467-020-17229-x
doi: 10.1038/s41467-020-17229-x pubmed: 32636384 pmcid: 7340788
Winston F, Carlson M (1992) Yeast SNF/SWI transcriptional activators and the SPT/SIN chromatin connection. Trends Genet 8:387–391. https://doi.org/10.1016/0168-9525(92)90300-s
doi: 10.1016/0168-9525(92)90300-s pubmed: 1332230
Ye Y, Wu H, Chen K, Clapier CR, Verma N, Zhang W, Deng H, Cairns BR, Gao N, Chen Z (2019) Structure of the RSC complex bound to the nucleosome. Science 366:838–843. https://doi.org/10.1126/science.aay0033
doi: 10.1126/science.aay0033 pubmed: 31672915 pmcid: 8442553
Yen K, Vinayachandran V, Batta K, Koerber RT, Pugh BF (2012) Genome-wide nucleosome specificity and directionality of chromatin remodelers. Cell 149:1461–1473. https://doi.org/10.1016/j.cell.2012.04.036
doi: 10.1016/j.cell.2012.04.036 pubmed: 22726434 pmcid: 3397793
Yudkovsky N, Logie C, Hahn S, Peterson CL (1999) Recruitment of the SWI/SNF chromatin remodeling complex by transcriptional activators. Genes Dev 13:2369–2374. https://doi.org/10.1101/gad.13.18.2369
doi: 10.1101/gad.13.18.2369 pubmed: 10500094 pmcid: 317021
Zhang M, Jungblut A, Kunert F, Hauptmann L, Hoffmann T, Kolesnikova O, Metzner F, Moldt M, Weis F, DiMaio F, Hopfner KP, Eustermann S (2023) Hexasome-INO80 complex reveals structural basis of noncanonical nucleosome remodeling. Science 381:313–319. https://doi.org/10.1126/science.adf6287
doi: 10.1126/science.adf6287 pubmed: 37384673

Auteurs

Eva-Carina Wendegatz (EC)

Center for Functional Genomics of Microbes, Institut Für Genetik Und Funktionelle Genomforschung, Universität Greifswald, Felix-Hausdorff-Strasse 8, 17487, Greifswald, Germany.

Maike Engelhardt (M)

Center for Functional Genomics of Microbes, Institut Für Genetik Und Funktionelle Genomforschung, Universität Greifswald, Felix-Hausdorff-Strasse 8, 17487, Greifswald, Germany.
Cheplapharm, Greifswald, Germany.

Hans-Joachim Schüller (HJ)

Center for Functional Genomics of Microbes, Institut Für Genetik Und Funktionelle Genomforschung, Universität Greifswald, Felix-Hausdorff-Strasse 8, 17487, Greifswald, Germany. schuell@uni-greifswald.de.

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