Abstract
In eukaryotes, DNA is packaged into chromatin, a compact structure that must be disrupted when genes are transcribed by RNA polymerase II. For transcription to take place, chromatin is remodeled via nucleosome disruption or displacement, a fundamental transcriptional regulatory mechanism in eukaryotic organisms. Here we show that the yeast chromatin-remodeling complex, RSC (remodels the structure of chromatin), isolated on the basis of homology to the SWI/SNF complex, is required for proper transcriptional regulation and nucleosome positioning in the highly inducible CHA1 promoter. In the absence of Sth1p/Nps1p (a homolog of Swi2p/Snf2p) or of Swh3p (a homolog of Swi3p), expression of CHA1 in non-induced cells is increased to a level comparable with that of fully induced cells. Furthermore, in non-induced cells depleted for Sth1p/Nps1p or Swh3p, a nucleosome positioned over the TATA box of the CHA1 promoter is disrupted, an architectural change normally only observed during transcriptional induction. In addition, deletion of the gene-specific activator Cha4p did not affect derepression of CHA1 in cells depleted for Swh3p. Thus, CHA1 constitutes a target for the RSC complex, and we propose that RSC is essential for maintaining a repressive chromatin structure at the CHA1 promoter.
Full Text
The Full Text of this article is available as a PDF (345.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bornaes C., Ignjatovic M. W., Schjerling P., Kielland-Brandt M. C., Holmberg S. A regulatory element in the CHA1 promoter which confers inducibility by serine and threonine on Saccharomyces cerevisiae genes. Mol Cell Biol. 1993 Dec;13(12):7604–7611. doi: 10.1128/mcb.13.12.7604. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buratowski S. The basics of basal transcription by RNA polymerase II. Cell. 1994 Apr 8;77(1):1–3. doi: 10.1016/0092-8674(94)90226-7. [DOI] [PubMed] [Google Scholar]
- Burns L. G., Peterson C. L. Protein complexes for remodeling chromatin. Biochim Biophys Acta. 1997 Feb 7;1350(2):159–168. doi: 10.1016/s0167-4781(96)00162-5. [DOI] [PubMed] [Google Scholar]
- Burns L. G., Peterson C. L. The yeast SWI-SNF complex facilitates binding of a transcriptional activator to nucleosomal sites in vivo. Mol Cell Biol. 1997 Aug;17(8):4811–4819. doi: 10.1128/mcb.17.8.4811. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cairns B. R. Chromatin remodeling machines: similar motors, ulterior motives. Trends Biochem Sci. 1998 Jan;23(1):20–25. doi: 10.1016/s0968-0004(97)01160-2. [DOI] [PubMed] [Google Scholar]
- Cairns B. R., Henry N. L., Kornberg R. D. TFG/TAF30/ANC1, a component of the yeast SWI/SNF complex that is similar to the leukemogenic proteins ENL and AF-9. Mol Cell Biol. 1996 Jul;16(7):3308–3316. doi: 10.1128/mcb.16.7.3308. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cairns B. R., Kim Y. J., Sayre M. H., Laurent B. C., Kornberg R. D. A multisubunit complex containing the SWI1/ADR6, SWI2/SNF2, SWI3, SNF5, and SNF6 gene products isolated from yeast. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1950–1954. doi: 10.1073/pnas.91.5.1950. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cairns B. R., Lorch Y., Li Y., Zhang M., Lacomis L., Erdjument-Bromage H., Tempst P., Du J., Laurent B., Kornberg R. D. RSC, an essential, abundant chromatin-remodeling complex. Cell. 1996 Dec 27;87(7):1249–1260. doi: 10.1016/s0092-8674(00)81820-6. [DOI] [PubMed] [Google Scholar]
- Cao Y., Cairns B. R., Kornberg R. D., Laurent B. C. Sfh1p, a component of a novel chromatin-remodeling complex, is required for cell cycle progression. Mol Cell Biol. 1997 Jun;17(6):3323–3334. doi: 10.1128/mcb.17.6.3323. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Corona D. F., Längst G., Clapier C. R., Bonte E. J., Ferrari S., Tamkun J. W., Becker P. B. ISWI is an ATP-dependent nucleosome remodeling factor. Mol Cell. 1999 Feb;3(2):239–245. doi: 10.1016/s1097-2765(00)80314-7. [DOI] [PubMed] [Google Scholar]
- Côté J., Peterson C. L., Workman J. L. Perturbation of nucleosome core structure by the SWI/SNF complex persists after its detachment, enhancing subsequent transcription factor binding. Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4947–4952. doi: 10.1073/pnas.95.9.4947. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Côté J., Quinn J., Workman J. L., Peterson C. L. Stimulation of GAL4 derivative binding to nucleosomal DNA by the yeast SWI/SNF complex. Science. 1994 Jul 1;265(5168):53–60. doi: 10.1126/science.8016655. [DOI] [PubMed] [Google Scholar]
- Du J., Nasir I., Benton B. K., Kladde M. P., Laurent B. C. Sth1p, a Saccharomyces cerevisiae Snf2p/Swi2p homolog, is an essential ATPase in RSC and differs from Snf/Swi in its interactions with histones and chromatin-associated proteins. Genetics. 1998 Nov;150(3):987–1005. doi: 10.1093/genetics/150.3.987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Durrin L. K., Mann R. K., Grunstein M. Nucleosome loss activates CUP1 and HIS3 promoters to fully induced levels in the yeast Saccharomyces cerevisiae. Mol Cell Biol. 1992 Apr;12(4):1621–1629. doi: 10.1128/mcb.12.4.1621. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Godde J. S., Nakatani Y., Wolffe A. P. The amino-terminal tails of the core histones and the translational position of the TATA box determine TBP/TFIIA association with nucleosomal DNA. Nucleic Acids Res. 1995 Nov 25;23(22):4557–4564. doi: 10.1093/nar/23.22.4557. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grunstein M. Histone function in transcription. Annu Rev Cell Biol. 1990;6:643–678. doi: 10.1146/annurev.cb.06.110190.003235. [DOI] [PubMed] [Google Scholar]
- Hayes J. J., Wolffe A. P. The interaction of transcription factors with nucleosomal DNA. Bioessays. 1992 Sep;14(9):597–603. doi: 10.1002/bies.950140905. [DOI] [PubMed] [Google Scholar]
- Hirschhorn J. N., Brown S. A., Clark C. D., Winston F. Evidence that SNF2/SWI2 and SNF5 activate transcription in yeast by altering chromatin structure. Genes Dev. 1992 Dec;6(12A):2288–2298. doi: 10.1101/gad.6.12a.2288. [DOI] [PubMed] [Google Scholar]
- Holmberg S., Schjerling P. Cha4p of Saccharomyces cerevisiae activates transcription via serine/threonine response elements. Genetics. 1996 Oct;144(2):467–478. doi: 10.1093/genetics/144.2.467. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Imbalzano A. N., Kwon H., Green M. R., Kingston R. E. Facilitated binding of TATA-binding protein to nucleosomal DNA. Nature. 1994 Aug 11;370(6489):481–485. doi: 10.1038/370481a0. [DOI] [PubMed] [Google Scholar]
- Ito T., Bulger M., Pazin M. J., Kobayashi R., Kadonaga J. T. ACF, an ISWI-containing and ATP-utilizing chromatin assembly and remodeling factor. Cell. 1997 Jul 11;90(1):145–155. doi: 10.1016/s0092-8674(00)80321-9. [DOI] [PubMed] [Google Scholar]
- Kadonaga J. T. Eukaryotic transcription: an interlaced network of transcription factors and chromatin-modifying machines. Cell. 1998 Feb 6;92(3):307–313. doi: 10.1016/s0092-8674(00)80924-1. [DOI] [PubMed] [Google Scholar]
- Kingston R. E., Bunker C. A., Imbalzano A. N. Repression and activation by multiprotein complexes that alter chromatin structure. Genes Dev. 1996 Apr 15;10(8):905–920. doi: 10.1101/gad.10.8.905. [DOI] [PubMed] [Google Scholar]
- Kruger W., Peterson C. L., Sil A., Coburn C., Arents G., Moudrianakis E. N., Herskowitz I. Amino acid substitutions in the structured domains of histones H3 and H4 partially relieve the requirement of the yeast SWI/SNF complex for transcription. Genes Dev. 1995 Nov 15;9(22):2770–2779. doi: 10.1101/gad.9.22.2770. [DOI] [PubMed] [Google Scholar]
- Kwon H., Imbalzano A. N., Khavari P. A., Kingston R. E., Green M. R. Nucleosome disruption and enhancement of activator binding by a human SW1/SNF complex. Nature. 1994 Aug 11;370(6489):477–481. doi: 10.1038/370477a0. [DOI] [PubMed] [Google Scholar]
- Laurent B. C., Yang X., Carlson M. An essential Saccharomyces cerevisiae gene homologous to SNF2 encodes a helicase-related protein in a new family. Mol Cell Biol. 1992 Apr;12(4):1893–1902. doi: 10.1128/mcb.12.4.1893. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laybourn P. J., Kadonaga J. T. Role of nucleosomal cores and histone H1 in regulation of transcription by RNA polymerase II. Science. 1991 Oct 11;254(5029):238–245. doi: 10.1126/science.254.5029.238. [DOI] [PubMed] [Google Scholar]
- Li G., Chandler S. P., Wolffe A. P., Hall T. C. Architectural specificity in chromatin structure at the TATA box in vivo: nucleosome displacement upon beta-phaseolin gene activation. Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4772–4777. doi: 10.1073/pnas.95.8.4772. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Logie C., Peterson C. L. Catalytic activity of the yeast SWI/SNF complex on reconstituted nucleosome arrays. EMBO J. 1997 Nov 17;16(22):6772–6782. doi: 10.1093/emboj/16.22.6772. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lorch Y., Cairns B. R., Zhang M., Kornberg R. D. Activated RSC-nucleosome complex and persistently altered form of the nucleosome. Cell. 1998 Jul 10;94(1):29–34. doi: 10.1016/s0092-8674(00)81218-0. [DOI] [PubMed] [Google Scholar]
- Lorch Y., Zhang M., Kornberg R. D. Histone octamer transfer by a chromatin-remodeling complex. Cell. 1999 Feb 5;96(3):389–392. doi: 10.1016/s0092-8674(00)80551-6. [DOI] [PubMed] [Google Scholar]
- Moreira J. M., Holmberg S. Nucleosome structure of the yeast CHA1 promoter: analysis of activation-dependent chromatin remodeling of an RNA-polymerase-II-transcribed gene in TBP and RNA pol II mutants defective in vivo in response to acidic activators. EMBO J. 1998 Oct 15;17(20):6028–6038. doi: 10.1093/emboj/17.20.6028. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Orphanides G., Lagrange T., Reinberg D. The general transcription factors of RNA polymerase II. Genes Dev. 1996 Nov 1;10(21):2657–2683. doi: 10.1101/gad.10.21.2657. [DOI] [PubMed] [Google Scholar]
- Paranjape S. M., Kamakaka R. T., Kadonaga J. T. Role of chromatin structure in the regulation of transcription by RNA polymerase II. Annu Rev Biochem. 1994;63:265–297. doi: 10.1146/annurev.bi.63.070194.001405. [DOI] [PubMed] [Google Scholar]
- Peterson C. L., Dingwall A., Scott M. P. Five SWI/SNF gene products are components of a large multisubunit complex required for transcriptional enhancement. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):2905–2908. doi: 10.1073/pnas.91.8.2905. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Phelan M. L., Sif S., Narlikar G. J., Kingston R. E. Reconstitution of a core chromatin remodeling complex from SWI/SNF subunits. Mol Cell. 1999 Feb;3(2):247–253. doi: 10.1016/s1097-2765(00)80315-9. [DOI] [PubMed] [Google Scholar]
- Schnitzler G., Sif S., Kingston R. E. Human SWI/SNF interconverts a nucleosome between its base state and a stable remodeled state. Cell. 1998 Jul 10;94(1):17–27. doi: 10.1016/s0092-8674(00)81217-9. [DOI] [PubMed] [Google Scholar]
- Sternberg P. W., Stern M. J., Clark I., Herskowitz I. Activation of the yeast HO gene by release from multiple negative controls. Cell. 1987 Feb 27;48(4):567–577. doi: 10.1016/0092-8674(87)90235-2. [DOI] [PubMed] [Google Scholar]
- Tjian R., Maniatis T. Transcriptional activation: a complex puzzle with few easy pieces. Cell. 1994 Apr 8;77(1):5–8. doi: 10.1016/0092-8674(94)90227-5. [DOI] [PubMed] [Google Scholar]
- Treich I., Cairns B. R., de los Santos T., Brewster E., Carlson M. SNF11, a new component of the yeast SNF-SWI complex that interacts with a conserved region of SNF2. Mol Cell Biol. 1995 Aug;15(8):4240–4248. doi: 10.1128/mcb.15.8.4240. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Treich I., Carlson M. Interaction of a Swi3 homolog with Sth1 provides evidence for a Swi/Snf-related complex with an essential function in Saccharomyces cerevisiae. Mol Cell Biol. 1997 Apr;17(4):1768–1775. doi: 10.1128/mcb.17.4.1768. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Treich I., Ho L., Carlson M. Direct interaction between Rsc6 and Rsc8/Swh3,two proteins that are conserved in SWI/SNF-related complexes. Nucleic Acids Res. 1998 Aug 15;26(16):3739–3745. doi: 10.1093/nar/26.16.3739. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Trouche D., Le Chalony C., Muchardt C., Yaniv M., Kouzarides T. RB and hbrm cooperate to repress the activation functions of E2F1. Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11268–11273. doi: 10.1073/pnas.94.21.11268. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsuchiya E., Hosotani T., Miyakawa T. A mutation in NPS1/STH1, an essential gene encoding a component of a novel chromatin-remodeling complex RSC, alters the chromatin structure of Saccharomyces cerevisiae centromeres. Nucleic Acids Res. 1998 Jul 1;26(13):3286–3292. doi: 10.1093/nar/26.13.3286. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Varga-Weisz P. D., Wilm M., Bonte E., Dumas K., Mann M., Becker P. B. Chromatin-remodelling factor CHRAC contains the ATPases ISWI and topoisomerase II. Nature. 1997 Aug 7;388(6642):598–602. doi: 10.1038/41587. [DOI] [PubMed] [Google Scholar]
- Walker G. M. Cell cycle specificity of certain antimicrotubular drugs in Schizosaccharomyces pombe. J Gen Microbiol. 1982 Jan;128(1):61–71. doi: 10.1099/00221287-128-1-61. [DOI] [PubMed] [Google Scholar]
- Wang W., Xue Y., Zhou S., Kuo A., Cairns B. R., Crabtree G. R. Diversity and specialization of mammalian SWI/SNF complexes. Genes Dev. 1996 Sep 1;10(17):2117–2130. doi: 10.1101/gad.10.17.2117. [DOI] [PubMed] [Google Scholar]
- Winston F., Carlson M. Yeast SNF/SWI transcriptional activators and the SPT/SIN chromatin connection. Trends Genet. 1992 Nov;8(11):387–391. doi: 10.1016/0168-9525(92)90300-s. [DOI] [PubMed] [Google Scholar]
- Workman J. L., Roeder R. G. Binding of transcription factor TFIID to the major late promoter during in vitro nucleosome assembly potentiates subsequent initiation by RNA polymerase II. Cell. 1987 Nov 20;51(4):613–622. doi: 10.1016/0092-8674(87)90130-9. [DOI] [PubMed] [Google Scholar]
