Stage specific expression of histone deacetylase 4 (HDAC4) during oogenesis and early preimplantation development in mice.

Oogenesis is a critical event in the formation of gametes, which transfer genomic information to the next generation. During this process, the gene expression pattern changes dramatically concomitant with genome remodeling, while the genomic information is stably maintained. Histone acetylation, the level of which is dramatically changed during oogenesis, has been implicated in the regulation of genome remodeling. In order to identify genes that are involved in the dynamic changes in histone acetylation levels during oogenesis, we performed suppressive subtraction hybridization (SSH) using unfertilized versus fertilized oocytes. Among the genes identified by SSH, we found histone deacetylase 4 (HDAC4), whose expression has been detected in only a few types of adult tissues. RT-PCR analysis revealed that the expression of HDAC4 was specific for full-grown oocytes. The HDAC4 transcript was barely detected in the growing oocytes, whereas it was readily detectable in fully grown oocytes. The expression was maintained at a high level until the MII stage, but decreased prominently after fertilization. Then, the expression level remained low until the morula stage. Immunocytochemistry localized the HDAC4 protein in the chromosome of fully grown oocytes. Although HDACs are most closely linked with transcriptional regulation owing to deacetylation of the core histones of the chromatin, previous studies have shown that all of the histone residues examined were highly acetylated in full-grown oocytes. Therefore, our results suggest that HDAC4 acts on a non-histone protein and plays a role in some other cellular functions of full-grown oocytes. To address this possibility, we examined the expression of p53BP1, which is associated with HDAC4 and plays a critical role in the DNA damage response. RT-PCR analysis revealed that p53BP1 was expressed specifically in fully grown oocytes, as was HDAC4. These results suggest that HDAC4 plays a role in stabilizing the genomes of fully grown oocytes.