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The PHD Domain of Np95 (mUHRF1) is involved in large-scale reorganization of pericentromeric heterochromatin

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Item Type:Article
Title:The PHD Domain of Np95 (mUHRF1) is involved in large-scale reorganization of pericentromeric heterochromatin
Creators Name:Papait, R. and Pistore, C. and Grazini, U. and Babbio, F. and Cogliati, S. and Pecoraro, D. and Brino, L. and Morand, A.L. and Dechampesme, A.M. and Spada, F. and Leonhardt, H. and McBlane, F. and Oudet, P. and Bonapace, I.M.
Abstract:Monitoring Editor: Yixian Zheng Heterochromatic chromosomal regions undergo large-scale reorganization and progressively aggregate, forming chromocenters. These are dynamic structures that rapidly adapt to various stimuli that influence gene expression patterns, cell cycle progression, and differentiation. Np95-ICBP90 (m- and h-UHRF1) is a histone binding protein expressed only in proliferating cells. During pericentromeric heterochromatin (PH) replication, Np95 specifically relocalizes to chromocenters where it highly concentrates in the replication factories that correspond to less compacted DNA. Np95 recruits HDAC and DNMT1 to PH and depletion of Np95 impairs PH replication. Here we show that Np95 causes large-scale modifications of chromocenters independently from the H3:K9 and H4:K20 trimethylation pathways, from the expression levels of HP1, from DNA methylation and from the cell cycle. The PHD domain is essential to induce this effect. The PHD domain is also required in vitro to increase access of a restriction enzyme to DNA packaged into nucleosomal arrays. We propose that the PHD domain of Np95-ICBP90 contributes to the opening and/or stabilization of dense chromocenter structures to support the recruitment of modifying enzymes - like HDAC and DNMT1 - required for the replication and formation of PH.
Keywords:Acetylation, CCAAT-Enhancer-Binding Proteins, Cell Cycle, Centromere, Chromatin, DNA Methylation, Heterochromatin, Histones, Biological Models, NIH 3T3 Cells, Nucleosomes, Tertiary Protein Structure, RNA Interference, Animals, Mice
Source:Molecular Biology of the Cell
ISSN:1059-1524
Publisher:American Society for Cell Biology
Volume:19
Number:8
Page Range:3554-3563
Date:1 August 2008
Additional Information:Copyright (c) 2008 by The American Society for Cell Biology
Official Publication:https://doi.org/10.1091/mbc.E07-10-1059
PubMed:View item in PubMed

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