Histone methyltransferase Smyd3 regulates early embryonic lineage commitment in mice.
SET and MYND domain-containing protein 3 (Smyd3) is a histone H3 lysine 4 (H3K4) di- and tri-methyltransferase that forms a transcriptional complex with RNA polymerase II and activates the transcription of oncogenes and cell cycle genes in human cancer cells. However, the study of Smyd3 in mammalian early embryonic development has not yet been addressed. In the present study, we investigated the expression pattern of Smyd3 in mouse preimplantation embryos and the effects of RNA interference (RNAi)-mediated Smyd3 repression on the development of mouse embryos. We showed that Smyd3 mRNA levels increased after the two-cell stage, peaked at the four-cell stage, and gradually decreased thereafter. Moreover, in two-cell to eight-cell embryos, SMYD3 staining was more intense in the nuclei than it was in the cytoplasm. In Smyd3-knockdown embryos, the percentage of inner cell mass (ICM)-derived colony formation and trophectoderm (TE)-derived cell attachment were significantly decreased, which resulted in a reduction in the number of viable offspring. Furthermore, the expression of Oct4 and Cdx2 during mid-preimplantation gene activation was significantly decreased in Smyd3-knockdown embryos. In addition, the transcription levels of ICM and epiblast markers, such as Oct4, Nanog, and Sox2, the transcription levels of primitive endoderm markers, such as Gata6, and the transcription levels of TE markers, such as Cdx2 and Eomes, were significantly decreased in Smyd3-knockdown blastocysts. These findings indicate that SMYD3 plays an important role in early embryonic lineage commitment and peri-implantation development through the activation of lineage-specific genes.
Laboratory of Reproductive BiologyGraduate School of Agriculture, Kyoto University, Kyoto 606-8052, JapanLaboratory of Animal and Genome Sciences SectionNational Institute of Radiological Sciences, Chiba 263-8555, JapanGraduate School of MedicineInstitute of Laboratory Animals, Kyoto University, Kyoto 606-8501, Japan.
Shinnosuke
S
Suzuki
Laboratory of Reproductive BiologyGraduate School of Agriculture, Kyoto University, Kyoto 606-8052, JapanLaboratory of Animal and Genome Sciences SectionNational Institute of Radiological Sciences, Chiba 263-8555, JapanGraduate School of MedicineInstitute of Laboratory Animals, Kyoto University, Kyoto 606-8501, Japan.
Yusuke
Y
Nozawa
Laboratory of Reproductive BiologyGraduate School of Agriculture, Kyoto University, Kyoto 606-8052, JapanLaboratory of Animal and Genome Sciences SectionNational Institute of Radiological Sciences, Chiba 263-8555, JapanGraduate School of MedicineInstitute of Laboratory Animals, Kyoto University, Kyoto 606-8501, Japan.
Satoshi
S
Tsukamoto
Laboratory of Reproductive BiologyGraduate School of Agriculture, Kyoto University, Kyoto 606-8052, JapanLaboratory of Animal and Genome Sciences SectionNational Institute of Radiological Sciences, Chiba 263-8555, JapanGraduate School of MedicineInstitute of Laboratory Animals, Kyoto University, Kyoto 606-8501, Japan.
Takehito
T
Kaneko
Laboratory of Reproductive BiologyGraduate School of Agriculture, Kyoto University, Kyoto 606-8052, JapanLaboratory of Animal and Genome Sciences SectionNational Institute of Radiological Sciences, Chiba 263-8555, JapanGraduate School of MedicineInstitute of Laboratory Animals, Kyoto University, Kyoto 606-8501, Japan.
Hiroshi
H
Imai
Laboratory of Reproductive BiologyGraduate School of Agriculture, Kyoto University, Kyoto 606-8052, JapanLaboratory of Animal and Genome Sciences SectionNational Institute of Radiological Sciences, Chiba 263-8555, JapanGraduate School of MedicineInstitute of Laboratory Animals, Kyoto University, Kyoto 606-8501, Japan oog1nao@kais.kyoto-u.ac.jp.
Naojiro
N
Minami
D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D000071616:CDX2 Transcription Factor; D010064:Embryo Implantation / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D034622:RNA Interference; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D000071616:CDX2 Transcription Factor; C487514:Cdx2 protein, mouse; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors; D011495:Histone-Lysine N-Methyltransferase; C582787:Smyd3 protein, mouse