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Transcription from the mouse mammary tumor virus (MMTV) promoter can be induced by glucocorticoids or progestins. Progesterone treatment of cultured cells carrying an integrated single copy of an MMTV transgene leads to recruitment of progesterone receptor (PR), SWI/SNF, and SNF2h-related complexes to MMTV promoter. Recruitment is accompanied by selective displacement of histones H2A and H2B from the nucleosome B. In nucleosomes assembled on promoter sequences, SWI/SNF displaces histones H2A and H2B from MMTV nucleosome B, but not from other MMTV nucleosomes or from an rDNA promoter nucleosome. Thus, the outcome of nucleosome remodeling by purified SWI/SNF depends on the DNA sequence. On the other hand, 5 min after hormone treatment, the cytoplasmic signaling cascade Src/Ras/Erk is activated via an interaction of PR with the estrogen receptor, which activates Src. As a consequence of Erk activation PR is phosphorylated, Msk1 is activated, and a ternary complex PR-Erk-Msk1 is recruited to MMTV nucleosome B. Msk1 phosphorylates H3 at serine 10, which is followed by acetylation at lysine 14, displacement of HP1γ, and recruitment of Brg1, PCAF, and RNA polymerase II. Blocking Erk activation or Msk1 activity prevents induction of the MMTV transgene. Thus, the rapid nongenomic effects of progestins are essential for their transcriptional effects on certain progestin target genes. In rat endometrial stromal cells, picomolar concentrations of progestins trigger the cross talk of PR with ERβ that activates the Erk and Akt kinase pathways leading to cell proliferation in the absence of direct transcriptional effects of the ligand-activated PR. Thus, depending on the cellular context rapid kinase activation and transcriptional effect play different roles in the physiological response to progestins. © 2006 New York Academy of Sciences.


Documento: Artículo
Título:Chromatin remodeling and control of cell proliferation by progestins via cross talk of progesterone receptor with the estrogen receptors and kinase signaling pathways
Autor:Vicent, G.P.; Ballaré, C.; Zaurin, R.; Saragüeta, P.; Beato, M.
Filiación:Centre de Regulació Genòmica (CRG), Universitat Pompeu Fabra (UPF), PRBB, Dr Aiguader 88, 08003 Barcelona, Spain
Instituto de Biología Y Medicina Experimental, CONICET, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina
Center for Genomic Regulation (C.R.G.), PRBB, Dr Aiguader 88, E-08003 Barcelona, Spain
Palabras clave:Chromatin; Histone H1; Kinases; Mouse mammary tumor virus; Progesterone receptor; Transcriptional regulation; adenosine triphosphate; cell nucleus receptor; DNA directed RNA polymerase III; estrogen receptor; gestagen; heterochromatin protein 1; histone acetyltransferase PCAF; histone H2A; histone H2B; histone H3; lysine; mitogen activated protein kinase; phosphotransferase; progesterone; progesterone receptor; protein kinase B; protein tyrosine kinase; Ras protein; regulator protein; ribosome DNA; steroid receptor; estrogen receptor; gestagen; progesterone receptor; protein kinase; binding kinetics; cell proliferation; chromatin assembly and disassembly; chromosome analysis; concentration (parameters); conference paper; cytoplasm; DNA sequence; endometrium cell; enzyme activation; enzyme activity; enzyme phosphorylation; gene sequence; hormonal regulation; human; minichromosome; mitosis inhibition; molecular interaction; Mouse mammary tumor oncovirus; nonhuman; nucleosome; outcome assessment; promoter region; protein protein interaction; protein purification; signal transduction; transcription regulation; transgene; animal; drug effect; gene expression regulation; genetics; metabolism; mouse; Mouse mammary tumor oncovirus; rat; review; Mouse mammary tumor virus; Rattus; Animals; Cell Proliferation; Chromatin Assembly and Disassembly; Gene Expression Regulation; Mammary Tumor Virus, Mouse; Mice; Progestins; Promoter Regions (Genetics); Protein Kinases; Rats; Receptors, Estrogen; Receptors, Progesterone; Signal Transduction
Página de inicio:59
Página de fin:72
Título revista:Annals of the New York Academy of Sciences
Título revista abreviado:Ann. New York Acad. Sci.
CAS:adenosine triphosphate, 15237-44-2, 56-65-5, 987-65-5; lysine, 56-87-1, 6899-06-5, 70-54-2; mitogen activated protein kinase, 142243-02-5; phosphotransferase, 9031-09-8, 9031-44-1; progesterone, 57-83-0; protein kinase B, 148640-14-6; protein tyrosine kinase, 80449-02-1; protein kinase, 9026-43-1; Progestins; Protein Kinases, EC; Receptors, Estrogen; Receptors, Progesterone


  • EISEN, J.A., SWEDER, K.S., HANAWALT, P.C., Evolution of the SNF2 family of proteins: Subfamilies with distinct sequences and functions (1995) Nucleic Acids Res, 23, pp. 2715-2723
  • HASSAN, A.H., PROCHASSON, P., NEELY, K.E., Function and selectivity of bromodomains in anchoring chromatin-modifying complexes to promoter nucleosomes (2002) Cell, 111, pp. 369-379
  • BOYER, L.A., LATEK, R.R., PETERSON, C.L., The SANT domain: A unique histone-tail-binding module? (2004) Nat. Rev. Mol. Cell. Biol, 5, pp. 158-163
  • FLANAGAN, J.F., MI, L.Z., CHRUSZCZ, M., Double chromodomains cooperate to recognize the methylated histone H3 tail (2005) Nature, 438, pp. 1181-1185
  • JENUWEIN, T., ALLIS, C.D., Translating the histone code (2001) Science, 293, pp. 1074-1080
  • STRAHL, B.D., ALLIS, C.D., The language of covalent histone modifications (2000) Nature, 403, pp. 41-45
  • AGALIOTI, T., CHEN, G., THANOS, D., Deciphering the transcriptional histone acetylation code for a human gene (2002) Cell, 111, pp. 381-392
  • JACOBSON, R.H., LADURNER, A.G., KING, D.S., TJIAN, R., Structure and function of a human TAFII250 double bromodomain module (2000) Science, 288, pp. 1422-1425
  • ROBINSON-RECHAVI, M., ESCRIVA GARCIA, H., LAUDET, V., The nuclear receptor superfamily (2003) J. Cell. Sci, 116, pp. 585-586
  • EVANS, R.M., The steroid and thyroid hormone receptor superfamily (1988) Science, 240, pp. 889-895
  • O'MALLEY, B.W., CONNEELY, O.M., Orphan receptors: In search of a unifying hypothesis for activation (1992) Mol. Endocrinol, 6, pp. 1359-1361
  • ZARET, K.S., YAMAMOTO, K.R., Reversible and persistent changes in chromatin structure accompany activation of a glucocorticoid-dependent enhancer element (1984) Cell, 38, pp. 29-38
  • CHANDLER, V.L., MALER, B.A., YAMAMOTO, K.R., DNA sequences bound specifically by glucocorticoid receptor in vitro render a heterologous promoter hormone responsive in vivo (1983) Cell, 33, pp. 489-499
  • PAYVAR, F., DEFRANCO, D., FIRESTONE, G.L., Sequence-specific binding of glucocorticoid receptor to MTV DNA at sites within and upstream of the transcribed region (1983) Cell, 35, pp. 381-392
  • SCHEIDEREIT, C., GEISSE, S., WESTPHAL, H.M., BEATO, M., The glucocorticoid receptor binds to defined nucleotide sequences near the promoter of mouse mammary tumour virus (1983) Nature, 304, pp. 749-752
  • CHALEPAKIS, G., ARNEMANN, J., SLATER, E., Differential gene activation by glucocorticoids and progestins through the hormone regulatory element of mouse mammary tumor virus (1988) Cell, 53, pp. 371-382
  • VON DER AHE, D., JANICH, S., SCHEIDEREIT, C., Glucocorticoid and progesterone receptors bind to the same sites in two hormonally regulated promoters (1985) Nature, 313, pp. 706-709
  • CATO, A.C., HENDERSON, D., PONTA, H., The hormone response element of the mouse mammary tumour virus DNA mediates the progestin and androgen induction of transcription in the proviral long terminal repeat region (1987) EMBO J, 6, pp. 363-368
  • RICHARD-FOY, H., HAGER, G.L., Sequence-specific positioning of nucleosomes over the steroid-inducible MMTV promoter (1987) EMBO J, 6, pp. 2321-2328
  • BRUGGEMEIER, U., ROGGE, L., WINNACKER, E.L., BEATO, M., Nuclear factor I acts as a transcription factor on the MMTV promoter but competes with steroid hormone receptors for DNA binding (1990) EMBO J, 9, pp. 2233-2239
  • KALFF, M., GROSS, B., BEATO, M., Progesterone receptor stimulates transcription of mouse mammary tumour virus in a cell-free system (1990) Nature, 344, pp. 360-362
  • TRUSS, M., BARTSCH, J., SCHELBERT, A., Hormone induces binding of receptors and transcription factors to a rearranged nucleosome on the MMTV promoter in vivo (1995) EMBO J, 14, pp. 1737-1751
  • BRÜGGEMEIER, U., KALFF, M., FRANKE, S., Ubiquitous transcription factor OTF-1 mediates induction of the mouse mammary tumour virus promoter through synergistic interaction with hormone receptors (1991) Cell, 64, pp. 565-572
  • PINA, B., BRUGGEMEIER, U., BEATO, M., Nucleosome positioning modulates accessibility of regulatory proteins to the mouse mammary tumor virus promoter (1990) Cell, 60, pp. 719-731
  • EISFELD, K., CANDAU, R., TRUSS, M., BEATO, M., Binding of NF1 to the MMTV promoter in nucleosomes: Influence of rotational phasing, translational positioning and histone H1 (1997) Nucleic Acids Res, 25, pp. 3733-3742
  • BARTSCH, J., TRUSS, M., BODE, J., BEATO, M., Moderate increase in histone acetylation activates the mouse mammary tumor virus promoter and remodels its nucleosome structure (1996) Proc. Natl. Acad. Sci. USA, 93, pp. 10741-10746
  • VENDITTI, P., DI CROCE, L., KAUER, M., Assembly of MMTV promoter minichromosomes with positioned nucleosomes precludes NF1 access but not restriction enzyme cleavage (1998) Nucleic Acids Res, 26, pp. 3657-3666
  • DI CROCE, L., KOOP, R., VENDITTI, P., Two-step synergism between the progesterone receptor and the DNA-binding domain of nuclear factor 1 on MMTV minichromosomes (1999) Mol. Cell, 4, pp. 45-54
  • TSUKIYAMA, T., WU, C., Purification and properties of an ATP-dependent nucleosome remodeling factor (1995) Cell, 83, pp. 1011-1020
  • VICENT, G.P., NACHT, A.S., SMITH, C.L., DNA instructed displacement of histones H2A and H2B at an inducible promoter (2004) Mol. Cell, 16, pp. 439-452
  • SPANGENBERG, C., EISFELD, K., STUNKEL, W., The mouse mammary tumour virus promoter positioned on a tetramer of histones H3 and H4 binds nuclear factor 1 and OTF1 (1998) J. Mol. Biol, 278, pp. 725-739
  • HORN, P.J., CARRUTHERS, L.M., LOGIE, C., Phosphorylation of linker histones regulates ATP-dependent chromatin remodeling enzymes (2002) Nat. Struct. Biol, 9, pp. 263-267
  • VICENT, G.P., MELIA, M.J., BEATO, M., Asymmetric binding of histone H1 stabilizes MMTV nucleosomes and the interaction of progesterone receptor with the exposed HRE (2002) J. Mol. Biol, 324, pp. 501-517
  • KOOP, R., DI CROCE, L., BEATO, M., Histone H1 enhances synergistic activation of the MMTV promoter in chromatin (2003) EMBO J, 22, pp. 588-599
  • BJORNSTROM, L., SJOBERG, M., Mechanisms of estrogen receptor signaling: Convergence of genomic and nongenomic actions on target genes (2005) Mol. Endocrinol, 19, pp. 833-842
  • MIGLIACCIO, A., PICCOLO, D., CASTORIA, G., Activation of the Src/p21ras/Erk pathway by progesterone receptor via cross-talk with estrogen receptor (1998) EMBO J, 17, pp. 2008-2018
  • BALLARE, C., UHRIG, M., BECHTOLD, T., Two domains of the progesterone receptor interact with the estrogen receptor and are required for progesterone activation of the c-Src/Erk pathway in mammalian cells (2003) Mol. Cell. Biol, 23, pp. 1994-2008
  • VICENT, G.P., BALLARE, C., NACHT, A.S., Induction of progesterone target genes requires activation of Erk and Msk kinases and phosphorylation of histone H3 (2006) Mol. Cell, , In press
  • VALLEJO, G., BALLARE, C., BARANAO, J.L., Progestin activation of nongenomic pathways via cross talk of progesterone receptor with estrogen receptor beta induces proliferation of endometrial stromal cells (2005) Mol. Endocrinol, 19, pp. 3023-3037


---------- APA ----------
Vicent, G.P., Ballaré, C., Zaurin, R., Saragüeta, P. & Beato, M. (2006) . Chromatin remodeling and control of cell proliferation by progestins via cross talk of progesterone receptor with the estrogen receptors and kinase signaling pathways. Annals of the New York Academy of Sciences, 1089, 59-72.
---------- CHICAGO ----------
Vicent, G.P., Ballaré, C., Zaurin, R., Saragüeta, P., Beato, M. "Chromatin remodeling and control of cell proliferation by progestins via cross talk of progesterone receptor with the estrogen receptors and kinase signaling pathways" . Annals of the New York Academy of Sciences 1089 (2006) : 59-72.
---------- MLA ----------
Vicent, G.P., Ballaré, C., Zaurin, R., Saragüeta, P., Beato, M. "Chromatin remodeling and control of cell proliferation by progestins via cross talk of progesterone receptor with the estrogen receptors and kinase signaling pathways" . Annals of the New York Academy of Sciences, vol. 1089, 2006, pp. 59-72.
---------- VANCOUVER ----------
Vicent, G.P., Ballaré, C., Zaurin, R., Saragüeta, P., Beato, M. Chromatin remodeling and control of cell proliferation by progestins via cross talk of progesterone receptor with the estrogen receptors and kinase signaling pathways. Ann. New York Acad. Sci. 2006;1089:59-72.