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

Roberto Papait, Christian Pistore, Ursula Grazini, Federica Babbio, Sara Cogliati, Daniela Pecoraro, Laurent Brino, Anne Laure Morand, Anne Marie Dechampesme, Fabio Spada, Heinrich Leonhardt, Fraser McBlane, Pierre Oudet, Ian Marc Bonapace

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Abstract

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.

Original languageEnglish
Pages (from-to)3554-3563
Number of pages10
JournalMolecular Biology of the Cell
Volume19
Issue number8
DOIs
Publication statusPublished - Aug 2008

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Papait, R., Pistore, C., Grazini, U., Babbio, F., Cogliati, S., Pecoraro, D., Brino, L., Morand, A. L., Dechampesme, A. M., Spada, F., Leonhardt, H., McBlane, F., Oudet, P., & Bonapace, I. M. (2008). The PHD domain of Np95 (mUHRF1) is involved in large-scale reorganization of pericentromeric heterochromatin. Molecular Biology of the Cell, 19(8), 3554-3563. https://doi.org/10.1091/mbc.E07-10-1059