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Many X-linked microRNAs escape meiotic sex chromosome inactivation

Nature Genetics volume 41, pages 488–493 (2009)Cite this article

Abstract

Meiotic sex chromosome inactivation (MSCI) during spermatogenesis is characterized by transcriptional silencing of genes on both the X and Y chromosomes in mid-to-late pachytene spermatocytes1. MSCI is believed to result from meiotic silencing of unpaired DNA because the X and Y chromosomes remain largely unpaired throughout first meiotic prophase2. However, unlike X-chromosome inactivation in female embryonic cells, where 25–30% of X-linked structural genes have been reported to escape inactivation3, previous microarray4- and RT-PCR5–based studies of expression of >364 X-linked mRNA-encoding genes during spermatogenesis have failed to reveal any X-linked gene that escapes the silencing effects of MSCI in primary spermatocytes. Here we show that many X-linked miRNAs are transcribed and processed in pachytene spermatocytes. This unprecedented escape from MSCI by these X-linked miRNAs suggests that they may participate in a critical function at this stage of spermatogenesis, including the possibility that they contribute to the process of MSCI itself, or that they may be essential for post-transcriptional regulation of autosomal mRNAs during the late meiotic and early postmeiotic stages of spermatogenesis.

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Figure 1: Heat map representing expression levels of 77 currently known X-linked miRNAs in 12 organs of adult mice.
Figure 2: Heat map representing expression levels of 77 X-linked miRNAs in developing testes and nine purified spermatogenic cell populations.
Figure 3: Three types of X-linked miRNAs grouped according to their expression patterns during spermatogenesis.
Figure 4: Localization of three X-linked miRNAs in adult mouse testes using locked nucleic acid–based miRNA in situ hybridization.
Figure 5: ChIP-qPCR analyses of interactions between RNA polymerase II (pol II) and three X-linked miRNA genes.

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Acknowledgements

We would like to thank D. Page for critically reading the manuscript and providing helpful suggestions. This study was supported by grants from the National Institutes of Health (HD048855 and HD050281 to W.Y., and HD046637 to J.R.M.).

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Author notes

  1. Rui Song and Seungil Ro: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, USA

    Rui Song, Seungil Ro, Jason D Michaels, Chanjae Park & Wei Yan

  2. Department of Biology, University of Texas at San Antonio, San Antonio, Texas, USA

    John R McCarrey

Authors
  1. Rui Song
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  2. Seungil Ro
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  3. Jason D Michaels
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  6. Wei Yan
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Contributions

R.S., S.R., J.D.M. and C.P. performed the experiments. W.Y. and J.R.M. designed the study and wrote the manuscript.

Corresponding author

Correspondence to Wei Yan.

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Supplementary Tables 1–4, Supplementary Figures 1–3 and Supplementary Methods (PDF 1091 kb)

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Song, R., Ro, S., Michaels, J. et al. Many X-linked microRNAs escape meiotic sex chromosome inactivation. Nat Genet 41, 488–493 (2009). https://doi.org/10.1038/ng.338

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