Setdb1-mediated H3K9 methylation is enriched on the inactive X and plays a role in its epigenetic silencing
- Author(s)
- Keniry, A; Gearing, LJ; Jansz, N; Liu, J; Holik, AZ; Hickey, PF; Kinkel, SA; Moore, DL; Breslin, K; Chen, K; Liu, R; Phillips, C; Pakusch, M; Biben, C; Sheridan, JM; Kile, BT; Carmichael, C; Ritchie, ME; Hilton, DJ; Blewitt, ME;
- Journal Title
- Epigenetics Chromatin
- Publication Type
- Journal Article
- Abstract
- BACKGROUND: The presence of histone 3 lysine 9 (H3K9) methylation on the mouse inactive X chromosome has been controversial over the last 15 years, and the functional role of H3K9 methylation in X chromosome inactivation in any species has remained largely unexplored. RESULTS: Here we report the first genomic analysis of H3K9 di- and tri-methylation on the inactive X: we find they are enriched at the intergenic, gene poor regions of the inactive X, interspersed between H3K27 tri-methylation domains found in the gene dense regions. Although H3K9 methylation is predominantly non-genic, we find that depletion of H3K9 methylation via depletion of H3K9 methyltransferase Set domain bifurcated 1 (Setdb1) during the establishment of X inactivation, results in failure of silencing for around 150 genes on the inactive X. By contrast, we find a very minor role for Setdb1-mediated H3K9 methylation once X inactivation is fully established. In addition to failed gene silencing, we observed a specific failure to silence X-linked long-terminal repeat class repetitive elements. CONCLUSIONS: Here we have shown that H3K9 methylation clearly marks the murine inactive X chromosome. The role of this mark is most apparent during the establishment phase of gene silencing, with a more muted effect on maintenance of the silent state. Based on our data, we hypothesise that Setdb1-mediated H3K9 methylation plays a role in epigenetic silencing of the inactive X via silencing of the repeats, which itself facilitates gene silencing through alterations to the conformation of the whole inactive X chromosome.
- Publisher
- BioMed Central
- Research Division(s)
- Molecular Medicine; Stem Cells And Cancer; Chemical Biology
- PubMed ID
- 27195021
- Publisher's Version
- https://doi.org/10.1186/s13072-016-0064-6
- Open Access at Publisher's Site
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Creation Date: 2016-06-15 12:27:24
Last Modified: 2016-06-15 02:40:28