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Such abnormalities occur in most solid tumors and also cause severe developmental defects and spontaneous abortions. In contrast to the imbalances in chromosome dose that cause pathologies, the difference in X-chromosome dose used to determine sexual fate across diverse species is well tolerated. Dosage compensation mechanisms have evolved in such species to balance X-chromosome gene expression between the sexes, allowing them to tolerate the difference in X-chromosome dose. This review analyzes the chromosome counting mechanism that tallies X-chromosome number to determine sex (XO male and XX hermaphrodite) in the nematode Caenorhabditis elegans and the associated dosage compensation mechanism that balances X-chromosome gene expression between the sexes. Dissecting the molecular mechanisms underlying X-chromosome counting has revealed how small quantitative differences in intracellular signals can be translated into dramatically different fates. Dissecting the process of X-chromosome dosage compensation has revealed the interplay between chromatin modification and chromosome structure in regulating gene expression over vast chromosomal territories.<\/jats:p>","DOI":"10.1093\/genetics\/iyab197","type":"journal-article","created":{"date-parts":[[2022,1,9]],"date-time":"2022-01-09T12:42:27Z","timestamp":1641732147000},"source":"Crossref","is-referenced-by-count":48,"title":["Mechanisms of sex determination and X-chromosome dosage compensation"],"prefix":"10.1093","volume":"220","author":[{"given":"Barbara J","family":"Meyer","sequence":"first","affiliation":[{"name":"Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720-3204, 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