Phosphorylation of CDK2 on threonine 160 influences silencing of sex chromosome during male meiosis.
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 noncoding RNAs were found to localize to the sex body and take part in influencing expression of sex chromosome genes. Cyclin-dependent kinase 2 (Cdk2 (-/-)) spermatocytes show incomplete sex chromosome pairing. Here, we further showed that phosphorylation of CDK2 isoform 1 (p-CDK2(39) [39 kDa]) on threonine 160 localizes to the sites of asynapsis and the sex body, interacting with phosphorylated gamma-H2AX. Meanwhile, p-CDK2(39) 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-CDK2(39) in influencing silencing of the sex chromosomes during male meiosis by interacting with gamma-H2AX.
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
Lu
L
Wang
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China College of Life Science and Technology, Southwest University of Science and Technology, Mianyang, Sichuan, China.
Wenjing
W
Liu
Engineering College of Animal Husbandry and Veterinary Science, Henan Agricultural University, Zhengzhou, Henan, China.
Weidong
W
Zhao
Engineering College of Animal Husbandry and Veterinary Science, Henan Agricultural University, Zhengzhou, Henan, China.
Gendi
G
Song
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
Guishuan
G
Wang
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
Xiaorong
X
Wang
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China feisun@ustc.edu.cn.
Fei
F
Sun
D000818:Animals; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics* / Q000378:metabolism; D020868:Gene Silencing / Q000502:physiology; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008540:Meiosis / Q000502:physiology*; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D010766:Phosphorylation / Q000235:genetics; D013090:Spermatocytes / Q000502:physiology; D013091:Spermatogenesis / Q000502:physiology; D013912:Threonine / Q000378:metabolism; D014960:X Chromosome / Q000235:genetics*; D049951:X Chromosome Inactivation / Q000502:physiology; D014998:Y Chromosome / Q000235:genetics*
D051357:Cyclin-Dependent Kinase 2; D006657:Histones; D013912:Threonine; C495893:Cdk2 protein, mouse; C475961:gamma-H2AX protein, mouse
MSCI; X chromosome; Y chromosome; histone modifications; kinases; meiosis; p-CDK239; spermatocyte; γ-H2AX