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Vol. 18, Issue 3, 1098-1106, March 2007
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Department of Structural and Functional Biology, University of Insubria, 21052 Busto Arsizio (VA), Italy
Submitted September 29, 2006;
Revised November 27, 2006;
Accepted November 30, 2006
Monitoring Editor: Wendy Bickmore
Heterochromatin plays an important role in transcriptional repression, for the correct segregation of chromosomes and in the maintenance of genome stability. Pericentric heterochromatin (PH) replication and formation have been proposed to occur in the pericentric heterochromatin duplication body (pHDB). A central question is how the underacetylated state of heterochromatic histone H4 tail is established and controlled, because it is a key event during PH replication and is essential to maintain the compacted and silenced state of these regions. Np95 is a cell cycle regulated and is a nuclear histone-binding protein that also recruits HDAC-1 to target promoters. It is essential for S phase and for embryonic formation and is implicated in chromosome stability. Here we show that Np95 is part of the pHDB, and its functional ablation causes a strong reduction in PH replication. Depletion of Np95 also causes a hyperacetylation of lysines 8, 12, and 16 of heterochromatin histone H4 and an increase of pericentromeric major satellite transcription, whose RNAs are key players for heterochromatin formation. We propose that Np95 is a new relevant protein involved in heterochromatin replication and formation.
The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).
Address correspondence to: Ian Marc Bonapace (ian.bonapace{at}uninsubria.it)
Abbreviations used: PH, pericentric heterochromatin; pHDB, pericentric heterochromatin duplication body; RNAi, RNA interference; siRNA, small interfering RNA.
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