Barbara J. Meyer
University of California, Berkeley
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Primary Section: 26, Genetics Secondary Section: 22, Cellular and Developmental Biology Membership Type:
Member
(elected 2000)
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Research Interests
My laboratory explores the mechanisms by which small quantitative differences in molecular signals are translated into alternative developmental fates and the means by which genetic regulatory hierarchies control developmental decisions. In numerous organisms the decision to become male or female is made by an X-chromosome counting mechanism that reliably distinguishes one X chromosome from two. We have dissected such a precise chromosome counting mechanism in molecular detail in the nematode C. elegans. The number of X chromosomes is communicated by a set of X-linked signal elements that promote female development by repressing a male-inducing sex-determination switch gene via two distinct, dose-dependent molecular mechanisms. Organisms that use X-chromosome-based strategies to determine sex must evolve mechanisms to ensure that males and females express equal levels of X-chromosome products. We have shown that X-chromosome gene dosage is compensated by a specialized protein complex that assembles on both X chromosomes of females to repress transcription by half. The complex includes conserved components of mitotic and meiotic machinery, indicating a mechanistic link between X-chromosome-wide gene expression, higher-order chromatin structure, and chromosome segregation during mitosis and meiosis. Recruitment of chromosome segregation proteins to the new task of regulating X-chromosome gene expression points to the evolutionary origin of nematode dosage compensation.
