Journal
SCIENCE
Volume 309, Issue 5735, Pages 768-771Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1113673
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- NIGMS NIH HHS [R01-GM58839] Funding Source: Medline
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In mammals, X-inactivation establishes X-chromosome dosage parity between mates and females. How X-chromosome counting regulates this process remains elusive, because neither the hypothesized inactivation blocking factor nor the required cis-elements have been defined. Here, a mouse knockout and transgenic analysis identified DNA sequences within the noncoding Tsix and Xite genes as numerators. Homozygous deficiency of Tsix resulted in chaotic choice and a variable number of inactive X's, whereas overdosage of TsixlXite inhibited X-inactivation. Thus, counting was affected by specific TsixlXite mutations, suggesting that counting is genetically separable from but molecularly coupled to choice. The mutations affect XX and XY cells differently, demonstrating that counting and choice are regulated not by one blocking factor, but by both a blocking and a competence factor.
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