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Publication : Dynamic replacement of histone H3 variants reprograms epigenetic marks in early mouse embryos.

First Author  Akiyama T Year  2011
Journal  PLoS Genet Volume  7
Issue  10 Pages  e1002279
PubMed ID  21998593 Mgi Jnum  J:178003
Mgi Id  MGI:5296998 Doi  10.1371/journal.pgen.1002279
Citation  Akiyama T, et al. (2011) Dynamic replacement of histone H3 variants reprograms epigenetic marks in early mouse embryos. PLoS Genet 7(10):e1002279
abstractText  Upon fertilization, reprogramming of gene expression is required for embryo development. This step is marked by DNA demethylation and changes in histone variant composition. However, little is known about the molecular mechanisms causing these changes and their impact on histone modifications. We examined the global deposition of the DNA replication-dependent histone H3.1 and H3.2 variants and the DNA replication-independent H3.3 variant after fertilization in mice. We showed that H3.3, a euchromatic marker of gene activity, transiently disappears from the maternal genome, suggesting erasure of the oocyte-specific modifications carried by H3.3. After fertilization, H3.2 is incorporated into the transcriptionally silent heterochromatin, whereas H3.1 and H3.3 occupy unusual heterochromatic and euchromatin locations, respectively. After the two-cell stage, H3.1 and H3.3 variants resume their usual respective locations on heterochromatin and euchromatin. Preventing the incorporation of H3.1 and H3.2 by knockdown of the histone chaperone CAF-1 induces a reciprocal increase in H3.3 deposition and impairs heterochromatin formation. We propose that the deposition of different H3 variants influences the functional organization of chromatin. Taken together, these findings suggest that dynamic changes in the deposition of H3 variants are critical for chromatin reorganization during epigenetic reprogramming.
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