Developmental switch of CREM function during spermatogenesis: from antagonist to activator


MAMMALIAN spermatogenesis consists of a series of complex developmental processes controlled by the pituitary–hypothalamic axis1. This flow of biochemical information is directly regulated by the adenylate cyclase signal transaction pathway2. We have previously described the CREM (cyclic AMP-responsive element modulator) gene which generates, by cell-specific splicing, alternative antagonists of the cAMP transcriptional response3. Here we report the expression of a novel CREM isoform (CREMτ) in adult testis. CREMτ differs from the previously characterized CREM antagonists by the coordinate insertion of two glutamine-rich domains that confer transcriptional activation function. During spermatogenesis there was an abrupt switch in CREM expression. In premeiotic germ cells CREM is expressed at low amounts in the antagonist form. Subsequently, from the pachytene spermatocyte stage onwards, a splicing event generates exclusively the CREMτ activator, which accumulates in extremely high amounts. This splicing-dependent reversal in CREM function represents an important example of developmental modulation in gene expression.

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  1. 1

    Santen, R. J. in Endocrinology and Metabolism (eds Felig, P., Baxter, J. D., Broadus, A. E. & Frohman, L. A.) 821–905 (McGraw-Hill, New York, 1987).

    Google Scholar 

  2. 2

    Ewing, L. L. & Robaire, B. Ann. N.Y. Acad. Sci. 564, 1–302 (1989).

    Article  Google Scholar 

  3. 3

    Foulkes, N. S., Borrelli, E. & Sassone-Corsi, P. Cell 64, 739–749 (1991).

    CAS  Article  Google Scholar 

  4. 4

    Hoeffler, J. P., Meyer, T. E., Yun, Y., Jameson, J. L. & Habener, J. F. Science 242, 1430–1433 (1988).

    ADS  CAS  Article  Google Scholar 

  5. 5

    Gonzalez, G. A. et al. Nature 337, 749–752 (1989).

    ADS  CAS  Article  Google Scholar 

  6. 6

    Foulkes, N. S., Laoide, B. M., Schlotter, F. & Sassone-Corsi, P. Proc. natn. Acad. Sci. U.S.A. 88, 5448–5452 (1991).

    ADS  CAS  Article  Google Scholar 

  7. 7

    Mellon, P. L., Clegg, C. H., Correll, L. A. & McKnight, G. S. Proc. natn. Acad. Sci. U.S.A. 86, 4887–4891 (1989).

    ADS  CAS  Article  Google Scholar 

  8. 8

    Gonzales, G. A., Menzel, P., Leonard, J., Fischer, W. & Montminy, M. R. Molec. cell. Biol. 11, 1306–1312 (1991).

    Article  Google Scholar 

  9. 9

    Courey, A. J. & Tjian, R. Cell 55, 887–898 (1989).

    Article  Google Scholar 

  10. 10

    Lee, C. Q., Yun, Y., Hoeffler, J. P. & Habener, J. F. EMBO J. 9, 4455–4465 (1990).

    CAS  Article  Google Scholar 

  11. 11

    Willison, K. & Ashworth, A. Trends Genet. 3, 351–355 (1987).

    Article  Google Scholar 

  12. 12

    Dym, M. in Histology Cell and Tissue Biology (ed. Weiss, L.) 1000–1053 (Elsevier Biomedical, New York, 1983).

    Google Scholar 

  13. 13

    Lyon, M. F. & Hawkes, S. G. Nature 227, 1217–1219 (1970).

    ADS  CAS  Article  Google Scholar 

  14. 14

    Moutier, R. in The Laboratory Animal in the Study of Reproduction (eds Antikatzides, T., Erichsen, S. & Spiegel, A.) 5–7 (Fischer, Stuttgart, 1976).

    Google Scholar 

  15. 15

    Beebe, S. J. et al. Molec. Endocrin. 4, 465–475 (1990).

    CAS  Article  Google Scholar 

  16. 16

    McKnight, G. S. et al. Recent Prog. Horm. Res. 44, 307–335 (1988).

    CAS  PubMed  Google Scholar 

  17. 17

    Auffray, C. & Rougeon, F. Eur. J. Biochem. 107, 303–314 (1980).

    CAS  Article  Google Scholar 

  18. 18

    Sassone-Corsi, P., Ransone, L. J., Lamph, W. W. & Verma, I. M. Nature 336, 692–694 (1988).

    ADS  CAS  Article  Google Scholar 

  19. 19

    Mather, J. P. Biol. Reprod. 23, 243–251 (1980).

    CAS  Article  Google Scholar 

  20. 20

    Kilpatrick, D. L., Borland, K. & Jin, D. F. Proc. natn. Acad. Sci. U.S.A. 84, 5695–5699 (1987).

    ADS  CAS  Article  Google Scholar 

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Foulkes, N., Mellström, B., Benusiglio, E. et al. Developmental switch of CREM function during spermatogenesis: from antagonist to activator. Nature 355, 80–84 (1992).

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