title: Np95 is implicated in pericentromeric heterochromatin replication and in major satellite silencing.
abstract: 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.
authors.affiliation: Department of Structural and Functional Biology, University of Insubria, 21052 Busto Arsizio (VA), Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Papait
authors.forename: Christian
authors.initials: C
authors.lastname: Pistore
authors.forename: Diego
authors.initials: D
authors.lastname: Negri
authors.forename: Daniela
authors.initials: D
authors.lastname: Pecoraro
authors.forename: Lisa
authors.initials: L
authors.lastname: Cantarini
authors.forename: Ian Marc
authors.initials: IM
authors.lastname: Bonapace
mesh_terms: D000107:Acetylation; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002503:Centromere / Q000378:metabolism*; D004261:DNA Replication; D004276:DNA, Satellite / Q000235:genetics*; D020868:Gene Silencing; D006570:Heterochromatin / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000172:deficiency / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016196:S Phase; D044767:Ubiquitin-Protein Ligases; D015854:Up-Regulation / Q000235:genetics
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004276:DNA, Satellite; D006570:Heterochromatin; D006657:Histones; D009687:Nuclear Proteins; D012333:RNA, Messenger; D044767:Ubiquitin-Protein Ligases; C117054:Uhrf1 protein, mouse; D008239:Lysine