作 者:王露、刘文静、赵卫东、宋根娣、王贵栓、王小蓉、孙斐
Abstract:
In mammalian meiosis, the X and Y chromosomes are largely unsynapsed and transcriptionally silenced during the pachytene stage of meiotic prophase (meiotic sex chromosome inactivation), forming a specialized nuclear territory called sex or XY body. An increasing number of proteins and non-coding RNAs were found to localize to the sex body and take part in influencing expression of sex chromosome genes. Cdk2 (cyclin-dependent kinase 2)-/- spermatocytes show incomplete sex chromosome pairing. Here, we further show that p-CDK239 (phosphorylation of CDK2 isoform 1 (39 kD) on threonine 160) localizes to the sites of asynapsis and the sex body, interacting with phosphorylated H2AX (gamma-H2AX). Meanwhile, p-CDK239 is frequently mislocalized throughout the sex body and meiotic sex chromosome inactivation is disrupted in PWK×C57BL/6J hybrid mice. Furthermore, pachytene spermatocytes treated with mevastatin (an inhibitor of p-CDK2) showed overexpression of sex chromosome-linked genes. Our results highlight an important role for p-CDK239 in influencing silencing of the sex chromosomes during male meiosis by interacting with gamma-H2AX.
DOI: 10.1095/biolreprod.113.116624
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