Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/106846
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Type: Journal article
Title: Setdb1-mediated H3K9 methylation is enriched on the inactive X and plays a role in its epigenetic silencing
Author: Keniry, A.
Gearing, L.J.
Jansz, N.
Liu, J.
Holik, A.Z.
Hickey, P.F.
Kinkel, S.A.
Moore, D.L.
Breslin, K.
Chen, K.
Liu, R.
Phillips, C.
Pakusch, M.
Biben, C.
Sheridan, J.M.
Kile, B.T.
Carmichael, C.
Ritchie, M.E.
Hilton, D.J.
Blewitt, M.E.
Citation: Epigenetics & Chromatin, 2016; 9(1):16=1-16-20
Publisher: BioMed Central
Issue Date: 2016
ISSN: 1756-8935
1756-8935
Statement of
Responsibility: 
Andrew Keniry, Linden J. Gearing, Natasha Jansz, Joy Liu, Aliaksei Z. Holik, Peter F. Hickey, Sarah A. Kinkel, Darcy L. Moore, Kelsey Breslin, Kelan Chen, Ruijie Liu, Catherine Phillips, Miha Pakusch, Christine Biben, Julie M. Sheridan, Benjamin T. Kile, Catherine Carmichael, Matthew E. Ritchie, Douglas J. Hilton and Marnie E. Blewitt
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.
Keywords: H3K9 methylation; X inactivation; epigenetic silencing; Setdb1
Rights: © 2016 Keniry et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
RMID: 0030058498
DOI: 10.1186/s13072-016-0064-6
Grant ID: http://purl.org/au-research/grants/nhmrc/1045936
http://purl.org/au-research/grants/arc/DP1096092
Appears in Collections:Animal and Veterinary Sciences publications

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