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MBC in Press, published online ahead of print December 20, 2006
Mol. Biol. Cell 10.1091/mbc.E06-09-0874

A more recent version of this article appeared on March 1, 2007
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Submitted on September 29, 2006
Revised on November 27, 2006
Accepted on November 30, 2006

Np95 Is Implicated in Pericentromeric Heterochromatin Replication and in Major Satellite Silencing

Roberto Papait, Christian Pistore, Diego Negri, Daniela Pecoraro, Lisa Cantarini, and Ian Marc Bonapace

Department of Structural and Functional Biology, University of Insubria, 21052 Busto Arsizio (VA), Italy

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, since it’s 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 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.

Address correspondence to: Ian Marc Bonapace (ian.bonapace{at}uninsubria.it)




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