PMID:15252119

Citation	Ishov, AM, Vladimirova, OV and Maul, GG (2004) Heterochromatin and ND10 are cell-cycle regulated and phosphorylation-dependent alternate nuclear sites of the transcription repressor Daxx and SWI/SNF protein ATRX. J. Cell. Sci. 117:3807-20
Abstract	Placing regulatory proteins into different multiprotein complexes should modify key cellular processes. Here, we show that the transcription repressor Daxx and the SWI/SNF protein ATRX are both associated with two intranuclear domains: ND10/PML bodies and heterochromatin. The accumulation of ATRX at nuclear domain 10 (ND10) was mediated by its interaction with the N-terminus of Daxx. Binding of this complex to ND10 was facilitated by the interaction of the Daxx C-terminus with SUMOylated promyelocytic leukemia protein (PML). Although ATRX was present at heterochromatin during the entire cell cycle, Daxx was actively recruited to this domain at the end of S-phase. The FACT-complex member structure-specific recognition protein 1 (SSRP1) accumulated at heterochromatin simultaneously with Daxx and accumulation of both proteins depended on ATRX phosphorylation. Both Daxx and SSRP1 were released from heterochromatin early in G(2) phase and Daxx was recruited back to ND10, indicating that both proteins localize to heterochromatin during a very short temporal window of the cell cycle. ATRX seems to assemble a repression multiprotein complex including Daxx and SSRP1 at heterochromatin during a specific stage of the cell cycle, whereas Daxx functions as an adapter for ATRX accumulation at ND10. A potential functional consequence of Daxx accumulation at heterochromatin was found in the S- to G(2)-phase transition. In Daxx(-/-) cells, S-phase was accelerated and the propensity to form double nuclei was increased, functional changes that could be rescued by Daxx reconstitution and that might be the basis for the developmental problems observed in Daxx knockout animals.
Links	PubMed Online version:10.1242/jcs.01230
Keywords	Animals; Antimetabolites/pharmacology; Bromodeoxyuridine/pharmacology; Carrier Proteins/physiology; Cell Cycle; Cell Line; Cell Nucleus/metabolism; Cells, Cultured; Chromatin/metabolism; DNA Helicases/metabolism; G2 Phase; Heterochromatin/metabolism; Heterochromatin/physiology; Immunoprecipitation; Intracellular Signaling Peptides and Proteins/physiology; Mice; Mice, Knockout; Mice, Transgenic; Models, Biological; Neoplasm Proteins/metabolism; Nuclear Proteins/metabolism; Nuclear Proteins/physiology; Phosphorylation; Protein Binding; Protein Structure, Tertiary; Protein-Serine-Threonine Kinases/metabolism; Retroviridae/genetics; S Phase; Time Factors; Transcription Factors/metabolism; Tumor Suppressor Proteins
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