Fertilized egg or totipotent zygote undergoes cleavage divisions to form a blastocyst, consisting of outer trophoectoderm cells and inner cell mass with pluripotent primitive ectoderm cells. Epigenetic reprogramming, erasure and maintenance of epigenetic modification, occurs during early embryogenesis. In 2004, we identified and characterized JMJD2A/JHDM3A, JMJD2B, JMJD2C, JMJD2D, JMJD2E and JMJD2F. JMJD2A, JMJD2B and JMJD2C share the common domain architecture with JmjN, JmjC, two PHD, and two TUDOR domains. In 2006, other groups characterized JMJD2 family members as the H3K9 and/or H3K36 histone demethylases. Here, comparative integromics analyses on JMJD2A, JMJD2B and JMJD2C were carried out. Mouse Jmjd2a was expressed in fertilized egg and 2-cell embryos, while human JMJD2A was expressed in undifferentiated and differentiated ES cells. AP1-binding site and six bHLH-binding sites within intron 13 of human JMJD2A gene were conserved in mouse Jmjd2a gene. Mouse Jmjd2b was expressed in 8-cell embryos and undifferentiated ES cells, while human JMJD2B was expressed in undifferentiated and differentiated ES cells. Two GATA-binding sites within intron 6 of human JMJD2B gene were conserved in mouse Jmjd2b gene. Mouse Jmjd2c and human JMJD2C were preferentially expressed in undifferentiated ES cells. Four NANOG-binding sites, one TCF/ LEF-binding site, and one bHLH-binding site were located within evolutionary conserved region at the 3'-flanking region of human JMJD2C gene. NANOG- TCF/LEF-, and bHLH-binding sites within the 3'-flanking region of human JMJD2C gene were conserved in chimpanzee, cow, mouse and rat JMJD2C othologs. Together these facts indicate that JMJD2C is the evolutionarily conserved target of Homeo-domain transcription factor NANOG, and that JMJD2C is the histone demethylase implicated in the epigenetic reprogramming during the early embryogenesis.

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