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. 1996 Jul 1;15(13):3394–3402.

The hbrm and BRG-1 proteins, components of the human SNF/SWI complex, are phosphorylated and excluded from the condensed chromosomes during mitosis.

C Muchardt 1, J C Reyes 1, B Bourachot 1, E Leguoy 1, M Yaniv 1
PMCID: PMC451903  PMID: 8670841

Abstract

In yeast, the SNF/SWI complex is believed to regulate transcription by locally altering the chromatin structure. At the present time, three human homologues of yeast SNF/SWI proteins have been characterized: hbrm and BRG-1, homologues of SNF2/SWI2, and hSNF5, a homologue of SNF5. We show here that, during mitosis, hbrm and BRG-1 are phosphorylated and excluded from the condensed chromosomes. In this phase of the cell cycle, the level of hbrm protein is also strongly reduced, whereas the level of BRG-1 remains constant. The mitotic phosphorylation of hbrm and BRG-1 is found not to disrupt the association of these proteins with hSNF5 but correlates with a decreased affinity for the nuclear structure in early M phase. We suggest that chromosomal exclusion of the human SNF/SWI complex at the G2-M transition could be part of the mechanism leading to transcriptional arrest during mitosis.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. 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]
  2. 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]
  3. Delmas V., Stokes D. G., Perry R. P. A mammalian DNA-binding protein that contains a chromodomain and an SNF2/SWI2-like helicase domain. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2414–2418. doi: 10.1073/pnas.90.6.2414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. Durfee T., Mancini M. A., Jones D., Elledge S. J., Lee W. H. The amino-terminal region of the retinoblastoma gene product binds a novel nuclear matrix protein that co-localizes to centers for RNA processing. J Cell Biol. 1994 Nov;127(3):609–622. doi: 10.1083/jcb.127.3.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hershkovitz M., Riggs A. D. Metaphase chromosome analysis by ligation-mediated PCR: heritable chromatin structure and a comparison of active and inactive X chromosomes. Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):2379–2383. doi: 10.1073/pnas.92.6.2379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Johnson T. C., Holland J. J. Ribonucleic acid and protein synthesis in mitotic HeLa cells. J Cell Biol. 1965 Dec;27(3):565–574. doi: 10.1083/jcb.27.3.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kalpana G. V., Marmon S., Wang W., Crabtree G. R., Goff S. P. Binding and stimulation of HIV-1 integrase by a human homolog of yeast transcription factor SNF5. Science. 1994 Dec 23;266(5193):2002–2006. doi: 10.1126/science.7801128. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. LITTAU V. C., ALLFREY V. G., FRENSTER J. H., MIRSKY A. E. ACTIVE AND INACTIVE REGIONS OF NUCLEAR CHROMATIN AS REVEALED BY ELECTRON MICROSCOPE AUTORADIOGRAPHY. Proc Natl Acad Sci U S A. 1964 Jul;52:93–100. doi: 10.1073/pnas.52.1.93. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Lin B. T., Gruenwald S., Morla A. O., Lee W. H., Wang J. Y. Retinoblastoma cancer suppressor gene product is a substrate of the cell cycle regulator cdc2 kinase. EMBO J. 1991 Apr;10(4):857–864. doi: 10.1002/j.1460-2075.1991.tb08018.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lüscher B., Eisenman R. N. Mitosis-specific phosphorylation of the nuclear oncoproteins Myc and Myb. J Cell Biol. 1992 Aug;118(4):775–784. doi: 10.1083/jcb.118.4.775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Martínez-Balbás M. A., Dey A., Rabindran S. K., Ozato K., Wu C. Displacement of sequence-specific transcription factors from mitotic chromatin. Cell. 1995 Oct 6;83(1):29–38. doi: 10.1016/0092-8674(95)90231-7. [DOI] [PubMed] [Google Scholar]
  18. Mittnacht S., Weinberg R. A. G1/S phosphorylation of the retinoblastoma protein is associated with an altered affinity for the nuclear compartment. Cell. 1991 May 3;65(3):381–393. doi: 10.1016/0092-8674(91)90456-9. [DOI] [PubMed] [Google Scholar]
  19. Muchardt C., Sardet C., Bourachot B., Onufryk C., Yaniv M. A human protein with homology to Saccharomyces cerevisiae SNF5 interacts with the potential helicase hbrm. Nucleic Acids Res. 1995 Apr 11;23(7):1127–1132. doi: 10.1093/nar/23.7.1127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. 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]
  23. PRESCOTT D. M., BENDER M. A. Synthesis of RNA and protein during mitosis in mammalian tissue culture cells. Exp Cell Res. 1962 Mar;26:260–268. doi: 10.1016/0014-4827(62)90176-3. [DOI] [PubMed] [Google Scholar]
  24. Pearson R. B., Kemp B. E. Protein kinase phosphorylation site sequences and consensus specificity motifs: tabulations. Methods Enzymol. 1991;200:62–81. doi: 10.1016/0076-6879(91)00127-i. [DOI] [PubMed] [Google Scholar]
  25. Peränen J., Rikkonen M., Käriäinen L. A method for exposing hidden antigenic sites in paraformaldehyde-fixed cultured cells, applied to initially unreactive antibodies. J Histochem Cytochem. 1993 Mar;41(3):447–454. doi: 10.1177/41.3.8429208. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Schoor M., Schuster-Gossler K., Gossler A. The Etl-1 gene encodes a nuclear protein differentially expressed during early mouse development. Dev Dyn. 1993 Jul;197(3):227–237. doi: 10.1002/aja.1001970307. [DOI] [PubMed] [Google Scholar]
  28. Segil N., Roberts S. B., Heintz N. Mitotic phosphorylation of the Oct-1 homeodomain and regulation of Oct-1 DNA binding activity. Science. 1991 Dec 20;254(5039):1814–1816. doi: 10.1126/science.1684878. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Songyang Z., Blechner S., Hoagland N., Hoekstra M. F., Piwnica-Worms H., Cantley L. C. Use of an oriented peptide library to determine the optimal substrates of protein kinases. Curr Biol. 1994 Nov 1;4(11):973–982. doi: 10.1016/s0960-9822(00)00221-9. [DOI] [PubMed] [Google Scholar]
  31. TAYLOR J. H. Nucleic acid synthesis in relation to the cell division cycle. Ann N Y Acad Sci. 1960 Oct 7;90:409–421. doi: 10.1111/j.1749-6632.1960.tb23259.x. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Templeton D. J. Nuclear binding of purified retinoblastoma gene product is determined by cell cycle-regulated phosphorylation. Mol Cell Biol. 1992 Feb;12(2):435–443. doi: 10.1128/mcb.12.2.435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Weis K., Rambaud S., Lavau C., Jansen J., Carvalho T., Carmo-Fonseca M., Lamond A., Dejean A. Retinoic acid regulates aberrant nuclear localization of PML-RAR alpha in acute promyelocytic leukemia cells. Cell. 1994 Jan 28;76(2):345–356. doi: 10.1016/0092-8674(94)90341-7. [DOI] [PubMed] [Google Scholar]
  35. Williams T., Admon A., Lüscher B., Tjian R. Cloning and expression of AP-2, a cell-type-specific transcription factor that activates inducible enhancer elements. Genes Dev. 1988 Dec;2(12A):1557–1569. doi: 10.1101/gad.2.12a.1557. [DOI] [PubMed] [Google Scholar]
  36. Wilson C. J., Chao D. M., Imbalzano A. N., Schnitzler G. R., Kingston R. E., Young R. A. RNA polymerase II holoenzyme contains SWI/SNF regulators involved in chromatin remodeling. Cell. 1996 Jan 26;84(2):235–244. doi: 10.1016/s0092-8674(00)80978-2. [DOI] [PubMed] [Google Scholar]
  37. 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]

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