[en] The human prolactin gene is mainly expressed in pituitary lactotrope cells, but transcription from an alternative, far upstream promoter was detected in lymphoid, placental and mammary cells. We describe the transcriptional activity in rat pituitary cells of the complete region separating the two promoters, using transient transfection experiments. A far upstream activating region was only functional in combination with the prolactin promoter. DNaseI protection experiments revealed, in addition to binding sites for the pituitary-specific factor Pit-1, sites (e.g. SD1) for several ubiquitous factors and one lymphoid-specific factor (SD4). A single copy of the ubiquitous site SD1 or the lymphoid-specific site SD4 was unable to activate transcription of a heterologous promoter in pituitary cells. However, SD1 activated transcription in nonpituitary cells and SD4 was functional specifically in lymphoid cells. Five copies of a distal site (D8) activated transcription in each cell type tested. Gel retardation experiments show that this site binds the specific factor C/EBP in liver and a distinct factor in other cell types. Our results suggest that different elements within this large region direct specific expression from each promoter via a complex interplay between cell-specific and ubiquitous transcription factors.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Van de Weerdt, Cécile ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Peers, Bernard ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Belayew, A.
Martial, Joseph ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Muller, Marc ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Language :
English
Title :
Far upstream sequences regulate the human prolactin promoter transcription
Nelson C, Albert VR, Elsholtz HP, Lu L-W, Rosenfeld MG: Activation of cell-specific expression of rat growth hormone and prolactin genes by a common transcription factor. Science 1988;239:1400-1405.
Mangalam HJ, Albert VR, Ingraham HA, Kapiloff M, Wilson L, Nelson C, Elsholtz H, Rosenfeld MG: A pituitary POU demain protein, Pit-1, activates both growth hormone and prolactin promoters transcriptionally. Genes Dev 1989;3:946-958.
Li S, Crenshaw EB, Rawson EJ, Simmons DM, Swanson LW, Rosenfeld MG: Dwarf locus mutants, which lack three pituitary cell types, result from mutations in the POU domain gene, Pit-1. Nature 1990;347:528-530.
Nelson C, Crenshaw EB, Franco R, Lira SA, Albert VR, Evans RM, Rosenfeld MG: Discrete cis-active genomic sequences dictate the pituitary cell type-specific expression of rat prolactin and growth hormone genes. Nature 1986;322:557-562.
Peers B, Voz ML, Monget P, Mathy-Hartert M, Berwaer M, Belayew A, Martial JA: Regulatory elements controlling pituitary-specific expression of the human prolactin gene. Mol Cell Biol 1990;10:4690-4700.
Berwaer M, Peers B, Nalda AM, Monget P, Davis JRE, Belayew A, Martial JA: Thyrotropin-releasing hormone and epidermal growth factor induce human prolactin expression via identical multiple cis elements. Mol Cell Endocrinol 1993;92:1-7.
Caccavelli L, Manfroid I, Martial JA, Muller M: Transcription factor AP-1 is involved in basal and okadaic acid stimulated activity of the human prolactin promoter. Mol Endocrinol 1998;12:1215-1227.
Nalda AM, Martial JA, Muller M: The glucocorticoid receptor inhibits the human prolactin gene expression by interference with Pit-1 activity. Mol Cell Endocrinol 1997;134:129-137.
Pernasetti F, Caccavelli L, van de Weerdt C, Martial JA, Muller M: Thyroid hormone inhibits the human prolactin gene promoter by interfering with activating protein-1 and estrogen stimulations. Mol Endocrinol 1997;11:986-996.
Dimattia GE, Gellersen B, Bohnet HG, Friesen HG: A human B-lymphoblastoid cell line produces prolactin. Endocrinology 1988;122: 2508-2517.
Gellersen B, Bonhoff A, Hunt N, Bonnet HG: Decidual-type prolactin expression by the human myometrium. Endocrinology 1991;129: 158-168.
Pelligrini I, Lebrun J-J, Ali S, Kelly P: Expression of prolactin and its receptor in human lymphoid cells. Mol Endocrinol 1992;6:1023-1031.
Sabharwal P, Glaser R, Lafuse W, Varma S, Liu Q, Aarkins S, Kooijam R, Kutz L, Kelley KW, Malarkey WB: Prolactin synthesized and secreted by human peripheral blood mononuclear cells: An autocrine growth factor for lymphoproliferation. Proc Natl Acad Sci USA 1992;89:7713-7716.
Dimattia GE, Gellersen B, Duckworth ML, Friesen HG: Human prolactin gene expression: The use of an alternative noncoding exon in decidua and the IM-9-P3 lymphoblast cell line. J Biol Chem 1990;265:16412-16421.
Gellersen B, Kempf R, Telgmann R, Dimattia GE: Nonpituitary human prolactin gene transcription is independent of Pit-1 and differentially controlled in lymphocytes and in endometrial stroma. Mol Endocrinol 1994;8:356-373.
Berwaer M, Martial JA, Davis JRE: Characterization of an upstream promoter directing extrapituitary expression of the human prolactin gene. Mol Endocrinol 1994;8:635-642.
Berwaer M, Monget P, Peers B, Mathy-Hartert M. Bellefroid E, Davis JR, Belayew A, Martial JA: Multihormonal regulation of the human prolactin gene expression from 5000 bp of its upstream sequence. Mol Cell Endocrinol 1991; 80:53-64.
Sanger F, Nicklen S, Coulson AR: DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 1977;74:5463-5467.
Luckow B, Schutz G: CAT constructions with multiple unique restriction sites for functional analysis of eukaryotic promoters and regulatory elements. Nucl Acids Res 1987;15:5490.
Macgregor GR, Caskey CT: Construction of plasmids that express E. coli β-galactosidase in mammalian cells. Nucleic Acids Res 1989;17: 2365.
Manley JL: Transcription of eukaryotic genes in a whole cell extract: in Hames BD, Higgins SJ (eds): Transcription and Translation - A practical Approach. Oxford, IRL Press, 1984, pp 71-87.
Landschulz WH, Johnson PF, Adashi EY, Graves BJ, McKnight SL: Isolation of a recombinant copy of the gene encoding C/EBP. Genes Dev 1988;7:786-800.
Lemaigre FP, Peers B, Lafontaine DA, Mathy-Harter M, Rousseau GG, Belayew A, Martial JA: Pituitary-specific factor binding to the human prolactin, growth hormone and placental lactogen genes. DNA 1989;8:149-159.
Ingraham HA, Chen R, Mangalam HJ, Elsholtz HP, Flynn SE, Lin CR, Simmons DM, Swanson L, Rosenfeld MG: A tissue-specific transcription factor containing a homeodomain specifies a pituitary phenotype. Cell 1988;55: 519-529.
Howell BW, Lagace M, Shore GC: Activity of the carbamyl phosphate synthetase I promoter in liver nuclear extracts is dependent on a cis-acting C/EBP recognition element. Mol Cell Biol 1989;9:2928-2933.
Crenshaw EB III, Kalla K, Simmons DM, Swanson LW, Rosenfeld MG: Cell-specific expression of the prolactin gene in transgenic mice is controlled by synergistic interactions between promoter and enhancer elements. Genes Dev 1989;3:959-972.
Baniahmad A, Muller M, Steiner C, Renkawitz R: Activity of two different silencer elements of the chicken lysozyme gene can be compensated by enhancer elements. EMBO J 1987;6:2297-2303.
Steiner C, Muller M, Baniahmad A, Renkawitz R: Lysozyme gene activity in chicken macrophages is controlled by positive and negative regulatory elements. Nucleic Acids Res 1987; 15:4163-4178.
Hammer RE, Krumlauf R, Camper SA, Brinster RL, Tilghman SM: Diversity of alpha-feto-protein gene expression in mice is generated by combination of separate enhancer elements. Science 1987;235:53-58.
Dimattia GE, Rhodes SJ, Krones A, Carrière C, O'Connell S, Kalla K, Arias C, Sawchenko P, Rosenfeld MG: The PIT-1 gene is regulated by distinct early and late pituitary-specific enhancers. Dev Biol 1997;182:180-190.
Delhase M, Castrillo J-L, De La Hoya M, Rajas F, Hooghe-Peters EL: AP-1 and Oct-1 transcription factors down-regulate the expression of the human Pit-1/GHF1 gene. J Biol Chem 1996;271:32349-32358.
Day RN, Koiske S, Sakan M, Muramatsu M, Maurer RA: Both Pit-1 and estrogen receptor are required for estrogen responsiveness of the rat prolactin gene. Mol Endocrinol 1990;4: 1964-1971.
Voss JW, Wilson L, Rosenfeld MG: POU-domain proteins Pit-1 and Oct-1 interact to form heteromeric complex and can cooperate to induce expression of the prolactin promoter. Genes Dev 1991;5:1309-1320.
Schaufele F, West BL, Baxter JD: Synergistic activation of the rat growth hormone promoter by Pit-1 and the thyroid hormone receptor. Mol Endocrinol 1992;6:656-665.
Kim MK, McClaskey JH, Bodenner DL, Weintrauh BD: An AP-1 like factor and the pituitary-specific factor Pit-1 are both necessary to mediate hormonal induction of the human thyrotropin B gene expression. J Biol Chem 1993; 268:23366-23375.
Lipkin SM, Näär AM, Kalla KA, Sack RA, Rosenfeld MG: Identification of a novel zinc finger protein binding a conversed element critical for Pit-1-dependent growth hormone gene expression. Genes Dev 1993;7:1674-1687.
Bach J, Rhodes SJ, Pearse RV, Heinzel T, Glass B, Scully KM, Sawchenko PE, Rosenfeld MG: P-Lim, A LIM homeodomain factor, is expressed during pituitary organ and cell commitment and synergizes with Pit-1. Proc Natl Acad Sci USA 1995;92:2720-2724.
Szeto DP, Ryan AK, O'Connell SM, Rosenfeld MG: P-OTX: A Pit-1 interacting homeodomain factor expressed during anterior pituitary gland development. Proc Natl Acad Sci USA 1996;93:7706-7710.
Bradford AP, Wasylik B, Gutierrez-Hartmann A: Interaction of Ets-1 and the POU-homeodomain protein GHF-1/Pit-1 reconstitutes pituitary-specific gene expression. Mol Cell Biol 1997;17:1065-1074.
Peers B, Monget P, Nalda AM, Voz ML, Berwaer M, Belayew A, Martial JA: Transcriptional induction of the human prolactin gene by cAMP requires two cis-acting elements and at least the pituitary-specific factor Pit-1. J Biol Chem 1991;266:18127-18134.
Verrijzer CP, Van Oosterhout JA, van Weperen WW, Van der Vliet PC: POU proteins bend DNA via the POU-specific domain. EMBO J 1991;10:3007-3014.
Muller M, Berwaer M, Caccavelli L, Manfroid I, Nalda A, Pendeville H, Pernasetti F, van de Weerdt C, Peers B, Martial JA: Regulation transcriptionnelle du gène de la prolactine humaine. Méd Sci 1998;14:580-587.
Gellersen B, Kempf R, Telgmann R, DiMattia GE: Pituitary-type transcription of the human prolactin gene in the absence of Pit-1. Mol Endocrinol 1995;9:887-901.
Gaasenbeek M, Gellersen B, DiMattia GE: DNasel hypersensitivity analysis of non-pituitary human prolactin gene expression. Mol Cell Endocrinol 1999;152:147-159.
Kuo CT, Leiden JM: Transcriptional regulation of T lymphocyte development and function. Annu Rev Immunol 1999;17:149-187.
