Inactive X chromosome

James Turner group project:

The role of MSUC and failure of MSCI in meiotic sterility

In both mice and humans, abnormalities in chromosome pairing are associated with meiotic sterility. We have shown that chromosomes unsynapsed during meiosis in the male and female are silencing by MSUC. MSUC provides a good explanation for how failure in chromosome synapsis causes meiotic arrest. For instance, in Turner syndrome mice (XO), the single X chromosome has no synaptic partner and this causes silencing of the whole X chromosome. We would predict that loss of X-linked products would be sufficient to cause arrest.

Conversely, escape from MSCI appears to be detrimental to meiosis. In XYY males, in which the Y chromosomes synapse and thereby escape MSCI, germ cells arrest during pachytene, and we predict that this is because of the toxic effects of expression of Y genes that should be silent during meiosis.

We are currently testing the role of MSUC, and of escape from MSCI, in meiotic sterility by genetically ablating silencing in different sex chromosomally aberrant mice and investigating whether this results in rescue of infertility.

Figure 1

Figure 1

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Transcriptional silencing of the X chromosome in XO oocytes. In XO oocyes, the single X chromosome has no synaptic partner (unlike in normal females which are XX). The unsynapsed X chromosome becomes enriched in γH2AX (arrow) and is transcriptionally repressed, as shown by Cot-1 RNA FISH, which highlights areas of ongoing transcription within the nucleus.

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