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Molecular basis of mammalian sexual determination: activation of Mullerian inhibiting substance gene expression by SRY
Abstract
The pathway of male sexual development in mammals is initiated by SRY, a gene on the short arm of the Y chromosome. Its expression in the differentiating gonadal ridge directs testicular morphogenesis, characterized by elaboration of Müllerian inhibiting substance (MIS) and testosterone. SRY and MIS each belong to conserved gene families that function in the control of growth and differentiation. Structural and biochemical studies of the DNA binding domain of SRY (the HMG box) revealed a protein-DNA interaction consisting of partial side chain intercalation into a widened minor groove. Functional studies of SRY in a cell line from embryonic gonadal ridge demonstrated activation of a gene-regulatory pathway leading to expression of MIS. SRY molecules containing mutations associated with human sex reversal have altered structural interactions with DNA and failed to induce transcription of MIS.
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Cites
Luo, X., Ikeda, Y., & Parker, K. L. (1994) · Cell · doi:10.1016/0092-8674(94)90211-9 · Cited by 1,631
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A male-specific role for SOX9 in vertebrate sex determination
Kent, J., Wheatley, S. C., Andrews, J. E., Sinclair, A. H., & Koopman, P. (1996) · Development · doi:10.1242/dev.122.9.2813 · Cited by 710
Mammalian sex determination: a molecular drama
Swain, A., & Lovell-Badge, R. (1999) · Genes & Development · doi:10.1101/gad.13.7.755 · Cited by 361
Reduced Ratio of Male to Female Births in Several Industrial Countries: A Sentinel Health Indicator?
Davis, D. L., Gottlieb, M. B., & Stampnitzky, J. R. (1998) · JAMA · doi:10.1001/jama.279.13.1018 · Cited by 313
Factors affecting birth weight in sheep: maternal environment
Gardner, D. S., Buttery, P. J., Daniel, Z., & Symonds, M. E. (2007) · Reproduction · doi:10.1530/rep-06-0042 · Cited by 243
Metadata
- Authors
- Haqq, C., King, C., Ukiyama, E., Falsafi, S., Haqq, T., Donahoe, P., & Weiss, M.
- Venue
- Science
- Published
- 1994-12-02
- Volume
- 266
- Issue
- 5190
- Pages
- 1494-1500
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2033304672
- Cited by
- 257
- References
- 1
- FWCI
- 16.13
- Type
- journal article
- Language
- en
- Open access
- closed
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- Haqq, C., King, C., Ukiyama, E., Falsafi, S., Haqq, T., Donahoe, P., & Weiss, M. (1994). Molecular basis of mammalian sexual determination: activation of Mullerian inhibiting substance gene expression by SRY. Science. https://doi.org/10.1126/science.7985018
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
