Epigenetic mechanisms are also involved in repressing expression of PGC genes in somatic cells. The repressive transcription factor E2F6 may be necessary to silence several PGC genes in somatic cells via DNA hypermethylation that locks the target promoters in transcriptionally inactive states. In addition, suppression of Oct4 expression in somatic cells by an orphan nuclear receptor, germ cell nuclear factor, depends on DNA hypermethylation of the Oct4 flanking region. Interestingly, in various types of human tumors, many testisspecific genes and PGC-specific genes are ectopically expressed, and CpG in the flanking regions are CpG-hypomethylated. Reportedly, the flanking regions of PGC-specific genes are generally CpG-hypermethylated in normal somatic tissues; these findings indicate that DNA demethylation activates ectopic expression in tumors. Taken together, these findings indicate that DNA methylation prevents ectopic expression of PGC-specific and/or pluripotentrelated genes in normal somatic cells. In addition, genome-wide DNA methylation analysis revealed that DNA methylation targeted to repress the germ cell related genes in pre- and post implantation epiblast; therefore, it is likely that there are epigenetic activating mechanisms that induce normal expression of specific genes in PGCs. Here, we focused on detailed epigenetic changes of representative genes preferentially expressed in PGCs and somatic genes, and a possible role of DNA demethylation in the expression of PGC genes that are Chlorhexidine hydrochloride initially expressed around the time of PGC fate determination was also investigated. Our findings indicated that the regions flanking PGC genes that contain the consensus element, ICE, commonly underwent DNA demethylated in differentiating PGCs after E9.0 in which the expression of those genes was upregulated. We also showed that repression of the Hox genes, representative somatic genes, as well as a neural cell-specific Gfap gene in PGCs was not dependent on DNA methylation, but may be regulated by the bivalent histone modification. During spermiogenesis, most histones are replaced with protamines, small basic proteins that form tightly packed DNA structures Pimozide important for normal sperm functions. Surprisingly, a few nucleosomes are retained in human sperm nuclei, and these nucleosomes are significantly enriched at loci of somatic genes, including HOX gene clusters, and they carry bivalent histone modification. Just after fertilization, paternal nuclei actively undergo DNA demethylation in genome-wide fashion. Hammoud et al. found that no genes with bivalent histone modification in sperms were found in the gene-set that was highly expressed in 4-cell or 8-cell human embryos. Hence, the bivalent histone modification in sperm nuclei may be a “safety devise” for appropriate gene expression even under the derepressive conditions of paternal nuclei in pre-implantation embryos. Although indepth experimental evidence showing functional importance of the bivalent histone modification in PGCs is not so far available, the above mentioned study implies that bivalent histone modification also repress somatic genes in hypomethylated DNA state 
observed in PGCs. These epigenetic modifications may be coordinated to permit the PGC-specific genes to be expressed during germ cell development and to poise other somatic genes for future activation at later stages. Current endocrine therapies for breast cancer patients target the estrogen receptor by reducing its ligand-induced activation, blocking its function and ultimately inducing ER degradation. Although these therapies are effective in many patients with ERpositive tumors, long-term follow up and clinical trials have demonstrated that up to 62% of breast cancers that are initially responsive to endocrine.