To monitor epigenetic changes, transcriptional activity and cell-cycle stages during primordial germ cell (PGC) migration, the authors mainly relied on immunohistochemistry, carried out in mice in which these cells are genetically marked with EGFP. Using antibodies against specific histone modifications, Seki et al. showed that as migration begins, around embryonic day E7.5, the levels of di- and monomethylated histone H3 lysine 9 (H3K9me2 and H3K9me1, respectively) — repressive marks — begin to drop and continue to do so until E8.75. But trimethylated histone H3 lysine 27 (H2K27me3) — another repressive mark — appeared elevated only at E8.25 and increased over time.
Given this erasure of H3K9me2 and H3K9me1, Seki et al. looked for a phosphorylated form of RNA polymerase II, which is associated with active transcription. Contrary to expectations, they found that its levels in PGCs were low at E8.75, suggesting that transcription is blocked in these cells. Using another antibody to detect the RNA polymerase II form that is associated with transition from transcriptional initiation to promoter clearance, the authors show that it is at this stage that transcription is blocked in PGCs. From these and other results, the authors propose that during migration PGCs become arrested at G2 phase of the cell cycle, their H3K9me2 levels drop and transcription is blocked (in a chromatin-independent manner); subsequently, H3K27me3 levels increase and transcription resumes approximately when PGCs are also released from the G2 arrest.
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