Letter | Published:

Tet1 controls meiosis by regulating meiotic gene expression

Nature volume 492, pages 443447 (20 December 2012) | Download Citation


Meiosis is a germ-cell-specific cell division process through which haploid gametes are produced for sexual reproduction1. Before the initiation of meiosis, mouse primordial germ cells undergo a series of epigenetic reprogramming steps2,3, including the global erasure of DNA methylation at the 5-position of cytosine (5mC) in CpG-rich DNA4,5. Although several epigenetic regulators, such as Dnmt3l and the histone methyltransferases G9a and Prdm9, have been reported to be crucial for meiosis6, little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. Using a loss-of-function approach in mice, here we show that the 5mC-specific dioxygenase Tet1 has an important role in regulating meiosis in mouse oocytes. Tet1 deficiency significantly reduces female germ-cell numbers and fertility. Univalent chromosomes and unresolved DNA double-strand breaks are also observed in Tet1-deficient oocytes. Tet1 deficiency does not greatly affect the genome-wide demethylation that takes place in primordial germ cells, but leads to defective DNA demethylation and decreased expression of a subset of meiotic genes. Our study thus establishes a function for Tet1 in meiosis and meiotic gene activation in female germ cells.

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Gene Expression Omnibus

Data deposits

RNA-seq and WGBS data have been deposited in the Gene Expression Omnibus under accession numbers GSE41908 and GSE41912, respectively.


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We thank J. Wang and W. Jiang for FACS sorting, A. Adey and J. Shendure for sharing reagents and protocols for Tn5mC-seq, and H.-L. Fung for Illumina sequencing. This work was partially supported by U01DK089565 (National Institutes of Health) (to Y.Z.), R01GM097253 and CIRM BRB3-05083 (to K.Z.). Y.Z. is an Investigator of the Howard Hughes Medical Institute. D.D. is a CIRM-UCSD pre-doctoral fellow.

Author information

Author notes

    • Shinpei Yamaguchi
    • , Kwonho Hong
    •  & Rui Liu

    These authors contributed equally to this work.


  1. Howard Hughes Medical Institute, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, Massachusetts 02115, USA

    • Shinpei Yamaguchi
    • , Kwonho Hong
    • , Li Shen
    • , Azusa Inoue
    •  & Yi Zhang
  2. Program in Cellular and Molecular Medicine, Boston Children’s Hospital, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, Massachusetts 02115, USA

    • Shinpei Yamaguchi
    • , Kwonho Hong
    • , Li Shen
    • , Azusa Inoue
    •  & Yi Zhang
  3. Department of Genetics, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, Massachusetts 02115, USA

    • Shinpei Yamaguchi
    • , Kwonho Hong
    • , Li Shen
    • , Azusa Inoue
    •  & Yi Zhang
  4. Departments of Bioengineering, University of California at San Diego, La Jolla, California 92093-0412 USA

    • Rui Liu
    • , Dinh Diep
    •  & Kun Zhang
  5. Harvard Stem Cell Institute, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, Massachusetts 02115, USA

    • Yi Zhang


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Y.Z. conceived the project; S.Y., K.H. and Y.Z. designed the experiments; S.Y., K.H., R.L., L.S. and A.I. performed the experiments; S.Y., K.H., R.L., D.D., K.Z. and Y.Z. analysed and interpreted the data; S.Y., K.H., R.L., K.Z. and Y.Z. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Kun Zhang or Yi Zhang.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains Supplementary Figures 1-20 and Supplementary Tables 1, 2, 4 and 7 (see separate files for Supplementary Tables 3, 5 and 6).

Excel files

  1. 1.

    Supplementary Table 3

    This file contains a list of differentially expressed genes (DEG) based on RNAseq.

  2. 2.

    Supplementary Table 5

    This table contains a List of differentially methylated regions (DMR) in female Tet1Gt/Gt PGC.

  3. 3.

    Supplementary Table 6

    This table contains a List of differentially expressed genes (DEG) associated with DMR.

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