SUMOylation promotes de novo targeting of HP1α to pericentric heterochromatin


HP1 enrichment at pericentric heterochromatin is considered important for centromere function. Although HP1 binding to H3K9me3 can explain its accumulation at pericentric heterochromatin, how it is initially targeted there remains unclear. Here, in mouse cells, we reveal the presence of long nuclear noncoding transcripts corresponding to major satellite repeats at the periphery of pericentric heterochromatin. Furthermore, we find that major transcripts in the forward orientation specifically associate with SUMO-modified HP1 proteins. We identified this modification as SUMO-1 and mapped it in the hinge domain of HP1α. Notably, the hinge domain and its SUMOylation proved critical to promote the initial targeting of HP1α to pericentric domains using de novo localization assays, whereas they are dispensable for maintenance of HP1 domains. We propose that SUMO-HP1, through a specific association with major forward transcript, is guided at the pericentric heterochromatin domain to seed further HP1 localization.

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Figure 1: Strand-specific localization of centromeric RNAs.
Figure 2: SUMO-1–modified HP1α interacts specifically with forward major RNAs.
Figure 3: SUMOylation of HP1α occurs at its hinge domain in vitro.
Figure 4: SUMOylation of HP1α promotes its targeting and accumulation at pericentric heterochromatin.
Figure 5: The hinge domain is required for de novo localization of HP1α at pericentric heterochromatin.
Figure 6: Model for a de novo HP1α targeting to pericentric heterochromatin.


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We thank A. Bird, D. Shapiro, R. Hay, T. Jenuwein, R. Losson and J. Seeler for constructs and reagents. We thank W. Faigle for mass spectrometry support, G. Cappello for helpful discussions, A. Cook for critical reading and P. Le Baccon at the Curie Imaging Platform. G.A.'s laboratory is funded by la Ligue Nationale contre le Cancer (Equipe labellisée la Ligue), Curie Programme Incitatif et Collaboratif (PIC) Programs, the European Network of Excellence Epigenome (LSHG-CT-2004-503433), ACI-2007-Cancéropôle IdF 'Breast cancer and Epigenetics', Agence Nationale de la Recherche (ANR) 'EcenS' ANR-09-BLAN-0257-01, INCa 'GepiG', European Research Council (ERC) Advanced Grant 2009-AdG-20090506, and D.L.'s laboratory was funded by le Cancéropôle Ile-de-France and l'INCA.

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C.M., J.-P.Q. and G.A. conceived and designed the experiments. C.M., D.B. and J.-P.Q. performed most of the experiments. D.R. and I.V. performed immuno-DNA FISH and immuno-RNA FISH. A.V.P. performed RNA FISH. F.D., B.L. and D.L. performed and analyzed mass spectrometry data using samples prepared by R.M.d.O. and they wrote together the corresponding parts. C.M. generated all figures. C.M., J.-P.Q. and G.A. analyzed the data. C.M. and G.A. wrote the paper. All authors contributed to final editing of the manuscript.

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Correspondence to Jean-Pierre Quivy or Geneviève Almouzni.

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Maison, C., Bailly, D., Roche, D. et al. SUMOylation promotes de novo targeting of HP1α to pericentric heterochromatin. Nat Genet 43, 220–227 (2011).

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