Abstract
The yeast and animal SNF-SWI and related multiprotein complexes are thought to play an important role in processes, such as transcription factor binding to regulatory elements, which require nucleosome remodeling in order to relieve the repressing effect of packaging DNA in chromatin. There are two mammalian homologs of the yeast SNF2-SWI2 subunit protein, SNF2alpha-brm and SNF2beta-BRG1, and overexpression of either one of them has been shown to enhance transcriptional activation by glucocorticoid, estrogen, and retinoic acid (RA) receptors in transiently transfected cells. We have investigated here the function of SNF2beta-BRG1 in the RA receptor-retinoid X receptor-mediated transduction of the retinoid signal in F9 embryonal carcinoma (EC) cells which differentiate into endodermal-like cells upon RA treatment. The two SNF2beta-BRG1 alleles have been targeted by homologous recombination and subsequently disrupted by using a conditional Cre recombinase. We show that F9 EC cells inactivated on both SNF2beta alleles are not viable and that heterozygous mutant cells are affected in proliferation but not in RA-induced differentiation. Thus, in F9 EC cells, SNF2beta-BRG1 appears to play an essential role in basal processes involved in cell proliferation, in addition to its putative role in the activation of transcription mediated by nuclear receptors.
Full Text
The Full Text of this article is available as a PDF (1.6 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ali S., Lutz Y., Bellocq J. P., Chenard-Neu M. P., Rouyer N., Metzger D. Production and characterization of monoclonal antibodies recognising defined regions of the human oestrogen receptor. Hybridoma. 1993 Aug;12(4):391–405. doi: 10.1089/hyb.1993.12.391. [DOI] [PubMed] [Google Scholar]
- Bouillet P., Oulad-Abdelghani M., Vicaire S., Garnier J. M., Schuhbaur B., Dollé P., Chambon P. Efficient cloning of cDNAs of retinoic acid-responsive genes in P19 embryonal carcinoma cells and characterization of a novel mouse gene, Stra1 (mouse LERK-2/Eplg2). Dev Biol. 1995 Aug;170(2):420–433. doi: 10.1006/dbio.1995.1226. [DOI] [PubMed] [Google Scholar]
- Boylan J. F., Lohnes D., Taneja R., Chambon P., Gudas L. J. Loss of retinoic acid receptor gamma function in F9 cells by gene disruption results in aberrant Hoxa-1 expression and differentiation upon retinoic acid treatment. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9601–9605. doi: 10.1073/pnas.90.20.9601. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boylan J. F., Lufkin T., Achkar C. C., Taneja R., Chambon P., Gudas L. J. Targeted disruption of retinoic acid receptor alpha (RAR alpha) and RAR gamma results in receptor-specific alterations in retinoic acid-mediated differentiation and retinoic acid metabolism. Mol Cell Biol. 1995 Feb;15(2):843–851. doi: 10.1128/mcb.15.2.843. [DOI] [PMC free article] [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., Levinson R. S., Yamamoto K. R., Kornberg R. D. Essential role of Swp73p in the function of yeast Swi/Snf complex. Genes Dev. 1996 Sep 1;10(17):2131–2144. doi: 10.1101/gad.10.17.2131. [DOI] [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]
- Carlson M., Laurent B. C. The SNF/SWI family of global transcriptional activators. Curr Opin Cell Biol. 1994 Jun;6(3):396–402. doi: 10.1016/0955-0674(94)90032-9. [DOI] [PubMed] [Google Scholar]
- Chambon P. A decade of molecular biology of retinoic acid receptors. FASEB J. 1996 Jul;10(9):940–954. [PubMed] [Google Scholar]
- Chiba H., Muramatsu M., Nomoto A., Kato H. Two human homologues of Saccharomyces cerevisiae SWI2/SNF2 and Drosophila brahma are transcriptional coactivators cooperating with the estrogen receptor and the retinoic acid receptor. Nucleic Acids Res. 1994 May 25;22(10):1815–1820. doi: 10.1093/nar/22.10.1815. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clifford J., Chiba H., Sobieszczuk D., Metzger D., Chambon P. RXRalpha-null F9 embryonal carcinoma cells are resistant to the differentiation, anti-proliferative and apoptotic effects of retinoids. EMBO J. 1996 Aug 15;15(16):4142–4155. [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]
- Dingwall A. K., Beek S. J., McCallum C. M., Tamkun J. W., Kalpana G. V., Goff S. P., Scott M. P. The Drosophila snr1 and brm proteins are related to yeast SWI/SNF proteins and are components of a large protein complex. Mol Biol Cell. 1995 Jul;6(7):777–791. doi: 10.1091/mbc.6.7.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dunaief J. L., Strober B. E., Guha S., Khavari P. A., Alin K., Luban J., Begemann M., Crabtree G. R., Goff S. P. The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest. Cell. 1994 Oct 7;79(1):119–130. doi: 10.1016/0092-8674(94)90405-7. [DOI] [PubMed] [Google Scholar]
- Elfring L. K., Deuring R., McCallum C. M., Peterson C. L., Tamkun J. W. Identification and characterization of Drosophila relatives of the yeast transcriptional activator SNF2/SWI2. Mol Cell Biol. 1994 Apr;14(4):2225–2234. doi: 10.1128/mcb.14.4.2225. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Elgin S. C. Heterochromatin and gene regulation in Drosophila. Curr Opin Genet Dev. 1996 Apr;6(2):193–202. doi: 10.1016/s0959-437x(96)80050-5. [DOI] [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]
- Ichinose H., Garnier J. M., Chambon P., Losson R. Ligand-dependent interaction between the estrogen receptor and the human homologues of SWI2/SNF2. Gene. 1997 Mar 25;188(1):95–100. doi: 10.1016/s0378-1119(96)00785-8. [DOI] [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]
- Imbalzano A. N., Schnitzler G. R., Kingston R. E. Nucleosome disruption by human SWI/SNF is maintained in the absence of continued ATP hydrolysis. J Biol Chem. 1996 Aug 23;271(34):20726–20733. doi: 10.1074/jbc.271.34.20726. [DOI] [PubMed] [Google Scholar]
- Khavari P. A., Peterson C. L., Tamkun J. W., Mendel D. B., Crabtree G. R. BRG1 contains a conserved domain of the SWI2/SNF2 family necessary for normal mitotic growth and transcription. Nature. 1993 Nov 11;366(6451):170–174. doi: 10.1038/366170a0. [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]
- 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., Carlson M. Yeast SNF2/SWI2, SNF5, and SNF6 proteins function coordinately with the gene-specific transcriptional activators GAL4 and Bicoid. Genes Dev. 1992 Sep;6(9):1707–1715. doi: 10.1101/gad.6.9.1707. [DOI] [PubMed] [Google Scholar]
- Laurent B. C., Treich I., Carlson M. The yeast SNF2/SWI2 protein has DNA-stimulated ATPase activity required for transcriptional activation. Genes Dev. 1993 Apr;7(4):583–591. doi: 10.1101/gad.7.4.583. [DOI] [PubMed] [Google Scholar]
- Le Douarin B., Nielsen A. L., Garnier J. M., Ichinose H., Jeanmougin F., Losson R., Chambon P. A possible involvement of TIF1 alpha and TIF1 beta in the epigenetic control of transcription by nuclear receptors. EMBO J. 1996 Dec 2;15(23):6701–6715. [PMC free article] [PubMed] [Google Scholar]
- Metzger D., Clifford J., Chiba H., Chambon P. Conditional site-specific recombination in mammalian cells using a ligand-dependent chimeric Cre recombinase. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6991–6995. doi: 10.1073/pnas.92.15.6991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moehrle A., Paro R. Spreading the silence: epigenetic transcriptional regulation during Drosophila development. Dev Genet. 1994;15(6):478–484. doi: 10.1002/dvg.1020150606. [DOI] [PubMed] [Google Scholar]
- Muchardt C., Reyes J. C., Bourachot B., Leguoy E., Yaniv M. The hbrm and BRG-1 proteins, components of the human SNF/SWI complex, are phosphorylated and excluded from the condensed chromosomes during mitosis. EMBO J. 1996 Jul 1;15(13):3394–3402. [PMC free article] [PubMed] [Google Scholar]
- Muchardt C., Yaniv M. A human homologue of Saccharomyces cerevisiae SNF2/SWI2 and Drosophila brm genes potentiates transcriptional activation by the glucocorticoid receptor. EMBO J. 1993 Nov;12(11):4279–4290. doi: 10.1002/j.1460-2075.1993.tb06112.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Okabe I., Bailey L. C., Attree O., Srinivasan S., Perkel J. M., Laurent B. C., Carlson M., Nelson D. L., Nussbaum R. L. Cloning of human and bovine homologs of SNF2/SWI2: a global activator of transcription in yeast S. cerevisiae. Nucleic Acids Res. 1992 Sep 11;20(17):4649–4655. doi: 10.1093/nar/20.17.4649. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Orlando V., Paro R. Chromatin multiprotein complexes involved in the maintenance of transcription patterns. Curr Opin Genet Dev. 1995 Apr;5(2):174–179. doi: 10.1016/0959-437x(95)80005-0. [DOI] [PubMed] [Google Scholar]
- Ostlund Farrants A. K., Blomquist P., Kwon H., Wrange O. Glucocorticoid receptor-glucocorticoid response element binding stimulates nucleosome disruption by the SWI/SNF complex. Mol Cell Biol. 1997 Feb;17(2):895–905. doi: 10.1128/mcb.17.2.895. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Owen-Hughes T., Utley R. T., Côté J., Peterson C. L., Workman J. L. Persistent site-specific remodeling of a nucleosome array by transient action of the SWI/SNF complex. Science. 1996 Jul 26;273(5274):513–516. doi: 10.1126/science.273.5274.513. [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]
- Pazin M. J., Kamakaka R. T., Kadonaga J. T. ATP-dependent nucleosome reconfiguration and transcriptional activation from preassembled chromatin templates. Science. 1994 Dec 23;266(5193):2007–2011. doi: 10.1126/science.7801129. [DOI] [PubMed] [Google Scholar]
- Peterson C. L., Herskowitz I. Characterization of the yeast SWI1, SWI2, and SWI3 genes, which encode a global activator of transcription. Cell. 1992 Feb 7;68(3):573–583. doi: 10.1016/0092-8674(92)90192-f. [DOI] [PubMed] [Google Scholar]
- Peterson C. L. Multiple SWItches to turn on chromatin? Curr Opin Genet Dev. 1996 Apr;6(2):171–175. doi: 10.1016/s0959-437x(96)80047-5. [DOI] [PubMed] [Google Scholar]
- Peterson C. L., Tamkun J. W. The SWI-SNF complex: a chromatin remodeling machine? Trends Biochem Sci. 1995 Apr;20(4):143–146. doi: 10.1016/s0968-0004(00)88990-2. [DOI] [PubMed] [Google Scholar]
- Quinn J., Fyrberg A. M., Ganster R. W., Schmidt M. C., Peterson C. L. DNA-binding properties of the yeast SWI/SNF complex. Nature. 1996 Feb 29;379(6568):844–847. doi: 10.1038/379844a0. [DOI] [PubMed] [Google Scholar]
- Randazzo F. M., Khavari P., Crabtree G., Tamkun J., Rossant J. brg1: a putative murine homologue of the Drosophila brahma gene, a homeotic gene regulator. Dev Biol. 1994 Jan;161(1):229–242. doi: 10.1006/dbio.1994.1023. [DOI] [PubMed] [Google Scholar]
- Richmond E., Peterson C. L. Functional analysis of the DNA-stimulated ATPase domain of yeast SWI2/SNF2. Nucleic Acids Res. 1996 Oct 1;24(19):3685–3692. doi: 10.1093/nar/24.19.3685. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Singh P., Coe J., Hong W. A role for retinoblastoma protein in potentiating transcriptional activation by the glucocorticoid receptor. Nature. 1995 Apr 6;374(6522):562–565. doi: 10.1038/374562a0. [DOI] [PubMed] [Google Scholar]
- Strickland S., Mahdavi V. The induction of differentiation in teratocarcinoma stem cells by retinoic acid. Cell. 1978 Oct;15(2):393–403. doi: 10.1016/0092-8674(78)90008-9. [DOI] [PubMed] [Google Scholar]
- Strickland S., Smith K. K., Marotti K. R. Hormonal induction of differentiation in teratocarcinoma stem cells: generation of parietal endoderm by retinoic acid and dibutyryl cAMP. Cell. 1980 Sep;21(2):347–355. doi: 10.1016/0092-8674(80)90471-7. [DOI] [PubMed] [Google Scholar]
- Strober B. E., Dunaief J. L., Guha, Goff S. P. Functional interactions between the hBRM/hBRG1 transcriptional activators and the pRB family of proteins. Mol Cell Biol. 1996 Apr;16(4):1576–1583. doi: 10.1128/mcb.16.4.1576. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tamkun J. W., Deuring R., Scott M. P., Kissinger M., Pattatucci A. M., Kaufman T. C., Kennison J. A. brahma: a regulator of Drosophila homeotic genes structurally related to the yeast transcriptional activator SNF2/SWI2. Cell. 1992 Feb 7;68(3):561–572. doi: 10.1016/0092-8674(92)90191-e. [DOI] [PubMed] [Google Scholar]
- Tsukiyama T., Daniel C., Tamkun J., Wu C. ISWI, a member of the SWI2/SNF2 ATPase family, encodes the 140 kDa subunit of the nucleosome remodeling factor. Cell. 1995 Dec 15;83(6):1021–1026. doi: 10.1016/0092-8674(95)90217-1. [DOI] [PubMed] [Google Scholar]
- Tsukiyama T., Wu C. Purification and properties of an ATP-dependent nucleosome remodeling factor. Cell. 1995 Dec 15;83(6):1011–1020. doi: 10.1016/0092-8674(95)90216-3. [DOI] [PubMed] [Google Scholar]
- Wall G., Varga-Weisz P. D., Sandaltzopoulos R., Becker P. B. Chromatin remodeling by GAGA factor and heat shock factor at the hypersensitive Drosophila hsp26 promoter in vitro. EMBO J. 1995 Apr 18;14(8):1727–1736. doi: 10.1002/j.1460-2075.1995.tb07162.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang W., Côté J., Xue Y., Zhou S., Khavari P. A., Biggar S. R., Muchardt C., Kalpana G. V., Goff S. P., Yaniv M. Purification and biochemical heterogeneity of the mammalian SWI-SNF complex. EMBO J. 1996 Oct 1;15(19):5370–5382. [PMC free article] [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]
- Wolffe A. P. Nucleosome positioning and modification: chromatin structures that potentiate transcription. Trends Biochem Sci. 1994 Jun;19(6):240–244. doi: 10.1016/0968-0004(94)90148-1. [DOI] [PubMed] [Google Scholar]
- Wolffe A. P. Transcription: in tune with the histones. Cell. 1994 Apr 8;77(1):13–16. doi: 10.1016/0092-8674(94)90229-1. [DOI] [PubMed] [Google Scholar]
- Xiao J. H., Davidson I., Matthes H., Garnier J. M., Chambon P. Cloning, expression, and transcriptional properties of the human enhancer factor TEF-1. Cell. 1991 May 17;65(4):551–568. doi: 10.1016/0092-8674(91)90088-g. [DOI] [PubMed] [Google Scholar]
- Yoshinaga S. K., Peterson C. L., Herskowitz I., Yamamoto K. R. Roles of SWI1, SWI2, and SWI3 proteins for transcriptional enhancement by steroid receptors. Science. 1992 Dec 4;258(5088):1598–1604. doi: 10.1126/science.1360703. [DOI] [PubMed] [Google Scholar]
- te Riele H., Maandag E. R., Clarke A., Hooper M., Berns A. Consecutive inactivation of both alleles of the pim-1 proto-oncogene by homologous recombination in embryonic stem cells. Nature. 1990 Dec 13;348(6302):649–651. doi: 10.1038/348649a0. [DOI] [PubMed] [Google Scholar]