Chromatin Remodeling Proteins Interact with Pericentrin to Regulate Centrosome Integrity

Program in Molecular Medicine, University of Massachusetts, Worcester, MA 01605, USA.
Molecular Biology of the Cell (Impact Factor: 4.47). 10/2007; 18(9):3667-80. DOI: 10.1091/mbc.E06-07-0604
Source: PubMed


Pericentrin is an integral centrosomal component that anchors regulatory and structural molecules to centrosomes. In a yeast two-hybrid screen with pericentrin we identified chromodomain helicase DNA-binding protein 4 (CHD4/Mi2beta). CHD4 is part of the multiprotein nucleosome remodeling deacetylase (NuRD) complex. We show that many NuRD components interacted with pericentrin by coimmunoprecipitation and that they localized to centrosomes and midbodies. Overexpression of the pericentrin-binding domain of CHD4 or another family member (CHD3) dissociated pericentrin from centrosomes. Depletion of CHD3, but not CHD4, by RNA interference dissociated pericentrin and gamma-tubulin from centrosomes. Microtubule nucleation/organization, cell morphology, and nuclear centration were disrupted in CHD3-depleted cells. Spindles were disorganized, the majority showing a prometaphase-like configuration. Time-lapse imaging revealed mitotic failure before chromosome segregation and cytokinesis failure. We conclude that pericentrin forms complexes with CHD3 and CHD4, but a distinct CHD3-pericentrin complex is required for centrosomal anchoring of pericentrin/gamma-tubulin and for centrosome integrity.

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Available from: Sambra Redick, Dec 26, 2014
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    • "Other examples of functional links between the centrosome and the nucleus are already present in literature. CHD3 and CHD4, which belong to the nucleosome remodeling deacetylase (NuRD) complex, interact with pericentrin to regulate centrosome integrity [47]. These results, if functionally validated, may reveal new roles for ciliary-associated transcripts. "
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    • "Maintenance of genome integrity is an essential process facilitated in eukarya by the nucleoprotein structures of chromatin. Multiple disease states result from mutation or aberrant function of enzymes dedicated to formation and/or maintenance of normal chromatin architecture, including the Mi-2/NuRD complex (Chou et al.; Cohet et al.; Larsen et al.; Misteli; Polo et al.; Smeenk et al.; Sillibourne et al., 2007; Pegoraro et al., 2009). Our results highlight the quality control processes engaged to monitor appropriate chromatin assembly ensuring that cells stably maintain their genomes. "
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    • "Other chromatin regulators have been involved in cell cycle processes unrelated to their transcriptional function. For example, chromatin-remodeling proteins were also found at human centrosomes, where they regulate the recruitment of centrosomal proteins, microtubule organization, and cytokinesis (Sillibourne et al., 2007). "
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