Expression of c-MYC in Nuclear Speckles During Mouse Oocyte Growth and Preimplantation Development

Abstract

Abstract. Myelocytomatosis oncogene (c-myc) is a major transcriptional regulator that controls various biological processes, and its deregulated expression causes carcinogenesis. To investigate the involvement of c-myc in oogenesis and preimplantation development, the expression of c-MYC during these stages was examined by immunocytochemistry. A strong c-MYC signal was detected in the nucleus of growing and fully grown oocytes as well as in preimplantation embryos before the morula stage. The signal intensity decreased slightly at the morula stage, and no signal was detected in blastocysts. Close observation of the nucleus revealed that c-MYC was localized in small granules that appeared to be nuclear speckles controlling pre-mRNA splicing. Although the number of granules decreased during oocyte growth, their size increased. After fertilization, the granules of c-MYC disappeared from the pronuclei, and c-MYC was evenly distributed in the nucleoplasm at the 1-cell stage, but the granules reappeared at the 2-cell stage. These results suggest that c-myc is involved in oocyte growth and preimplantation development and that its role changes during these stages. . It is ubiquitously expressed in normal tissues, but in some tumor cells, its expression is highly elevated or deregulated [2,3]. While this overexpression is not sufficient for induction of oncogenic transformation, it contributes to the process [4,5]. In normal cells, c-myc plays various important roles in cell survival, including transcriptional regulation, and the gene product, c-MYC protein contains both a leucine zipper and helix-loop-helix motifs, which allow it to bind to specific target sequences [6][7][8]; moreover, it forms a heterodimer with a protein called MAX, which is necessary for DNA binding, leading to the up-or downregulation of target gene transcription [9]. In addition, c-MYC is involved in DNA replication via a mechanism that does not involve transcriptional activation [10]. The suppression of c-myc expression by antisense RNA or specific antibodies inhibits DNA synthesis [11,12]. Furthermore, c-myc is involved in various other cellular functions, such as chromatin modification, apoptosis, and differentiation [13].C-MYC is an essential factor for normal embryonic development and differentiation. For example, suppression of c-MYC expression by antisense oligonucleotides reduces the developmental rate at the blastocyst stage in vitro [14], and a null mutation in cmyc results in embryonic lethality before day 10.5 in vivo [15]. However, the role of c-myc in oogenesis and early preimplantation development remains to be elucidated. Although c-myc RNA has been shown to be expressed during oocyte growth and preimplantation development, no data exist regarding the expression of c-MYC during these stages. In oocytes and early preimplantation embryos, the expression patterns of certain proteins are different from those of the transcripts, since the translation of maternal mRNA is posttranscriptionally regulated in a complex manner [16,17].In the ...

Global Gene Silencing is Caused by the Dissociation of RNA Polymerase II from DNA in Mouse Oocytes

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H3K27me3 may be associated with Oct4 and Sox2 in mouse preimplantation embryos

“…These gene expression profiles may have been caused by demethylation of H3K27 during the blastocyst stage. However, no c-Myc signal was detected in blastocysts (Suzuki et al, 2009). A previous study reported that the Ezh2 protein was observed in ICM cells according to immunofluorescence results (Zhang et al, 2009), indicating that Ezh2 and development-related genes are co-localized in mouse blastocysts.…”

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