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Maison C.,University Pierre and Marie Curie | Maison C.,French National Center for Scientific Research | Bailly D.,University Pierre and Marie Curie | Bailly D.,French National Center for Scientific Research | And 18 more authors.
Nature Genetics | Year: 2011

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. © 2011 Nature America, Inc. All rights reserved.

Muller S.,University Pierre and Marie Curie | Muller S.,French National Center for Scientific Research | Muller S.,Equipe Labellisee Ligue contre le Cancer | Muller S.,Paris-Sorbonne University | And 16 more authors.
Cell Reports | Year: 2014

Centromeres, epigenetically defined by the presence of the histone H3 variant CenH3, are essential for ensuring proper chromosome segregation. In mammals, centromeric CenH3CENP-A deposition requires its dedicated chaperone HJURP and occurs during telophase/early G1. We find that the cell-cycle-dependent recruitment of HJURP to centromeres depends on its timely phosphorylation controlled via cyclin-dependent kinases. A nonphosphorylatable HJURP mutant localizes prematurely to centromeres in S and G2 phase. This unregulated targeting causes a premature loading of CenH3CENP-A at centromeres, and cell-cycle delays ensue. Once recruited to centromeres, HJURP functions to promote CenH3CENP-A deposition by a mechanism involving a unique DNA-binding domain. With our findings, we propose amodel wherein (1) the phosphorylation state of HJURP controls its centromeric recruitment in acell-cycle-dependent manner, and (2) HJURP binding to DNA is a mechanistic determinant in CenH3CENP-A loading. © 2014 The Authors.

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