QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 13 July 2004
doi: 10.1242/jcs.01230

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.01230v1 117/17/3807    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ishov, A. M. Articles by Maul, G. G. Search for Related Content PubMed PubMed Citation Articles by Ishov, A. M. Articles by Maul, G. G.

Heterochromatin and ND10 are cell-cycle regulated and phosphorylation-dependent alternate nuclear sites of the transcription repressor Daxx and SWI/SNF protein ATRX

Alexander M. Ishov^*, Olga V. Vladimirova and Gerd G. Maul

The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA

Author for correspondence (e-mail: maul{at}wistar.upenn.edu)

Accepted 19 March 2004

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 G₂ 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 G₂-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.

Key words: Nuclear structure, ND10, Heterochromatin, Daxx, ATRX, SSRP1

This article has been cited by other articles:

				V. Lukashchuk, S. McFarlane, R. D. Everett, and C. M. Preston Human Cytomegalovirus Protein pp71 Displaces the Chromatin-Associated Factor ATRX from Nuclear Domain 10 at Early Stages of Infection J. Virol., December 15, 2008; 82(24): 12543 - 12554. [Abstract] [Full Text] [PDF]

				Q. Tang and G. G. Maul Mouse cytomegalovirus crosses the species barrier with help from a few human cytomegalovirus proteins. J. Virol., August 1, 2006; 80(15): 7510 - 7521. [Abstract] [Full Text] [PDF]

				J. J. Luciani, D. Depetris, Y. Usson, C. Metzler-Guillemain, C. Mignon-Ravix, M. J. Mitchell, A. Megarbane, P. Sarda, H. Sirma, A. Moncla, et al. PML nuclear bodies are highly organised DNA-protein structures with a function in heterochromatin remodelling at the G2 phase J. Cell Sci., June 15, 2006; 119(12): 2518 - 2531. [Abstract] [Full Text] [PDF]

				S.-L. Tzeng, Y.-W. Cheng, C.-H. Li, Y.-S. Lin, H.-C. Hsu, and J.-J. Kang Physiological and Functional Interactions between Tcf4 and Daxx in Colon Cancer Cells J. Biol. Chem., June 2, 2006; 281(22): 15405 - 15411. [Abstract] [Full Text] [PDF]

				C. M. Preston and M. J. Nicholl Role of the cellular protein hDaxx in human cytomegalovirus immediate-early gene expression. J. Gen. Virol., May 1, 2006; 87(Pt 5): 1113 - 1121. [Abstract] [Full Text] [PDF]

				G. Dellaire, C. H. Eskiw, H. Dehghani, R. W. Ching, and D. P. Bazett-Jones Mitotic accumulations of PML protein contribute to the re-establishment of PML nuclear bodies in G1 J. Cell Sci., March 15, 2006; 119(6): 1034 - 1042. [Abstract] [Full Text] [PDF]

				H.-Y. Kuo, C.-C. Chang, J.-C. Jeng, H.-M. Hu, D.-Y. Lin, G. G. Maul, R. P. S. Kwok, and H.-M. Shih SUMO modification negatively modulates the transcriptional activity of CREB-binding protein via the recruitment of Daxx PNAS, November 22, 2005; 102(47): 16973 - 16978. [Abstract] [Full Text] [PDF]

				R. M. Scaife Selective and irreversible cell cycle inhibition by diphenyleneiodonium Mol. Cancer Ther., June 1, 2005; 4(6): 876 - 884. [Abstract] [Full Text] [PDF]

				J. G. Greger, R. A. Katz, A. M. Ishov, G. G. Maul, and A. M. Skalka The Cellular Protein Daxx Interacts with Avian Sarcoma Virus Integrase and Viral DNA To Repress Viral Transcription J. Virol., April 15, 2005; 79(8): 4610 - 4618. [Abstract] [Full Text] [PDF]

				C.-C. Chang, D.-Y. Lin, H.-I Fang, R.-H. Chen, and H.-M. Shih Daxx Mediates the Small Ubiquitin-like Modifier-dependent Transcriptional Repression of Smad4 J. Biol. Chem., March 18, 2005; 280(11): 10164 - 10173. [Abstract] [Full Text] [PDF]

				D. P. Steensma, R. J. Gibbons, and D. R. Higgs Acquired {alpha}-thalassemia in association with myelodysplastic syndrome and other hematologic malignancies Blood, January 15, 2005; 105(2): 443 - 452. [Abstract] [Full Text] [PDF]

				Q. Tang, L. Li, and G. G. Maul Mouse Cytomegalovirus Early M112/113 Proteins Control the Repressive Effect of IE3 on the Major Immediate-Early Promoter J. Virol., January 1, 2005; 79(1): 257 - 263. [Abstract] [Full Text] [PDF]