ATRX Plays a Key Role in Maintaining Silencing at Interstitial Heterochromatic Loci and Imprinted Genes

• DOI: 10.1016/j.celrep.2015.03.036
• Publication Date: 2015-04-11T11:43:56Z
• Authors: Hsiao P.J. Voon; Jim R. Hughes; Christina Rode; Inti A. De La Ros...; Thomas Jenuwein; Robert Feil; Douglas R. Higgs; Richard J. Gibbons
• Keywords: ATRX; Genomic Imprinting

Histone H3.3 is a replication-independent histone variant, which replaces histones that are turned over throughout the entire cell cycle. deposition at euchromatin dependent on HIRA, whereas ATRX/Daxx deposits pericentric heterochromatin and telomeres. The role of heterochromatic regions unknown, but mutations in ATRX/Daxx/H3.3 pathway linked to aberrant telomere lengthening certain cancers. In this study, we show ATRX-dependent not limited telomeres also occurs sites genome. Notably, ATRX/H3.3 specifically localizes silenced imprinted alleles mouse ESCs. ATRX KO cells failed deposit these sites, leading loss H3K9me3 modification, repression, allelic expression. We propose model whereby into normally required maintain memory silencing loci.