Mutated elements of a complex promoter (Amh) can help to demonstrate the role of certain elements in controlling differential gene expression

David W. Dresser

The Ashworth Laboratory, The University of Edinburgh, Edinburgh, UK.

DOI: 10.4236/ajmb.2012.24036                

Abstract

Amh is a single copy gene which is expressed in different ways during mammalian development. Several potential promoter elements have been identified using physiological experimentation and on the basis of interspecific sequence comparison. The role of putative promoter elements in controlling gene expression has been investigated by many workers over the last two decades and here by individually mutating each element. Expression was measured in vitro in cells of Sertoli descent by flowcytometry using EGFP as a reporter gene. Three lines of murine cells were used; pre- and post-pubertal Sertoli and granulosa cells. Differences between the three lines of cells, support the view that differentiation in this in vitro model system is likely to be at the level of available transcription factors at given points in development.

Keywords

Anti-Mullerian Hormone; SDM; Site Directed Mutation; Murine; SMAT-1; TM4; Sertoli Cell Lines; KK1; Granulosa Cell Line

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Josso, N., Picard, J.Y., Rey, R. and di Clemente, N. (2006). Testicular anti-Mullerian hormone: history, genetics, regulation and clinical applications. Pediatr Endo-crinol Rev 3 , pp. 347-58.
[2]	Munsterberg, A. and Lovell-Badge, R. (1991). Expression of the mouse anti-mullerian hormone gene suggests a role in both male and female sexual differentiation. Development 113, pp. 613-24.
[3]	Hacker, A., Capel, B., Goodfellow, P. and Lovell-Badge, R. (1995). Expression of Sry, the mouse sex determining gene. Development 121 , pp. 1603-14.
[4]	Beau, C., Rauch, M., Joulin, V., Jegou, B. and Guerrier, D. (2000). GATA-1 is a potential repressor of anti-Mullerian hormone expression during the establishment of puberty in the mouse. Mol Reprod Dev 56 , pp. 124-38. doi:10.1002/(SICI)1098-2795(200006)56:2<124::AID-MRD2>3.0.CO;2-J
[5]	Durlinger, A.L., Visser, J.A. and Themmen, A.P. (2002). Regulation of ovarian function: the role of anti-Mullerian hormone. Reproduction 124, pp. 601-9. doi:10.1530/rep.0.1240601
[6]	Havelock, J.C., Rainey, W.E. and Carr, B.R. (2004). Ovarian granulosa cell lines. Mol Cell Endocrinol 228 ), pp. 67-78. doi:10.1016/j.mce.2004.04.018
[7]	Anttonen, M., Ketola, I,. Parvianen, H., {usa, A-K., Heikinheimo, M. (2003). FOG-2 and GATA- 4-4 are expressed in the mouse ovary and can modulate Mullerian-inhibiting substance expression. Biol Reprod. 68, pp1333-40.
[8]	Belville, C., Jamin, S.P., Picard, J.Y., Josso, N. and di Clemente, N. (2005). Role of type I receptors for anti-Mullerian hormone in the SMAT-1 Sertoli cell line. Oncogene 24, pp. 4984-92. doi:10.1038/sj.onc.1208686
[9]	Dresser, D.W. and Guerrier, D. (2005). Candidate Sertoli cell ]specific promoter element for a TGFbeta family member (Amh) and a 3' UTR enhancer/repressor for the same gene. Gene 363 , pp. 159-65. doi:10.1016/j.gene.2005.08.004
[10]	Medvinsky, A.L., Samoylina, N.L., Muller, A.M. and Dzierzak, E.A. (1993). An early pre-liver intraembryonic source of CFU-S in the developing mouse. Nature 364, pp. 64-7. doi:10.1038/364064a0
[11]	Vandevar, M.A., Weiner, M.P., Hutton, C.J. and Batt, C.A. (1988).A simple and rapid method for the selection of oligodeoxynucleotide-directed mutants. Gene 65, pp. 129-33. doi:10.1016/0378-1119(88)90425-8
[12]	Ho, S.N., Hunt, H.D., Horton, R.M., Pullen, J.K. and Pease, L.R. (1989). Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene 77, pp. 51-9. doi:10.1016/0378-1119(89)90358-2
[13]	Dresser, D.W., Hacker, A., Lovell-Badge, R. and Guerrier, D. (1995). The genes for a spliceosome protein (Sap 62) and the anti-Mullerian Hormone are contiguous. Hum.Molec.Genet. 4, pp. 613-618. doi:10.1093/hmg/4.9.1613
[14]	de Santa Barbara, P., Moniot, B., Poulat, F. and Berta, P. (2000). Expression and subcellular localization of SF-1, SOX9, WT1, and AMH proteins during early human tes-ticular development. Dev Dyn 217, pp. 293-8. doi:10.1002/(SICI)1097-0177(200003)217:3<293::AID-DVDY7>3.0.CO;2-P
[15]	Klattig, J., Sierig, R., Kruspe, D., Besenbeck, B. and Englert, C. (2007). Wilms' tumor protein Wt1 is an activator of the anti-Mullerian hormone receptor gene Amhr2. Mol Cell Biol 27, pp. 4355-64. doi:10.1128/MCB.01780-06
[16]	Mazaud Guittot, S., Tetu, A., Legault, E., Pilon, N., Silversides, D.W. and Viger, R.S. (2007). The proximal Gata4 promoter directs reporter gene expression to sertoli cells during mouse gonadal development. Biol Reprod 76, pp. 85-95. doi:10.1095/biolreprod.106.055137
[17]	Oreal, E., Mazaud, S., Picard, J.Y., Magre, S. and Carre-Eusebe, D. (2002). Different patterns of anti-Mullerian hormone expression, as related to DMRT1, SF-1, WT1, GATA-4, Wnt-4, and Lhx9 expression, in the chick differentiating gonads. Dev Dyn 225, pp. 221-32. doi:10.1002/dvdy.10153
[18]	Viger, R.S., Taniguchi, H., Robert, N.M. and Tremblay, J.J. (2004). Role of the GATA family of transcription factors in andrology. J Androl 25, pp. 441-52.
[19]	Schepers, G., Wilson, M., Wilhelm, D. and Koopman, P. (2003). SOX8 is expressed during testis differentiation in mice and synergizes with SF1 to activate the Amh promoter in vitro. J Biol Chem 278, pp. 28101-8. doi:10.1074/jbc.M304067200
[20]	Arango, N.A., Lovell-Badge, R. and Behringer, R.R. (1999). Targeted mutagenesis of the endogenous mouse Mis gene promoter: in vivo definition of genetic pathways of vertebrate sexual development. Cell 99, pp. 409-19. doi:10.1016/S0092-8674(00)81527-5
[21]	Escudero, J.M., Haller, J.L., Clay, C.M. and Escudero, K.W. (2010). Microarray analysis of Foxl2 mediated gene regulation in the mouse ovary derived KK1 granulosa cell line: Over-expression of Foxl2 leads to activation of the gonadotropin releasing hormone… J.Ovarian Res. 3:4. doi:10.1186/1757-2215-3-4
[22]	Koopman, P., Gubbay, J., Vivian, N., Goodfellow, P. and Lovell-Badge, R. (1991). Male development of chromosomally female mice transgenic for Sry. Nature 351, pp. 117-21. doi:10.1038/351117a0
[23]	Simmler, M.C., Cunningham, D.B., Clerc, P., Vermat, T]., Caudron, B., Cruaud, C., Pawlak, A., Szpirer, C., Weis-senbach, J., Claverie, J.M. and Avner, P. (1996). A 94 kb genomic sequence 3' to the murine Xist gene reveals an AT rich region containing a new testis specific gene Tsx. Hum Mol Genet 5, pp. 1713-26. doi:10.1093/hmg/5.11.1713