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Published online 9 August 2004. doi:10.1083/jcb.200403109
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 166, Number 4, 493-505
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Article

Mouse centric and pericentric satellite repeats form distinct functional heterochromatin



Mounia Guenatri, Delphine Bailly, Christèle Maison, and Geneviève Almouzni

Institut Curie/Research section, UMR218 du Centre National pour la Recherche Scientifique, 75248 Paris Cedex 05, France

Address correspondence to G. Almouzni, Institut Curie/Research section, UMR218 du Centre National pour la Recherche Scientifique, 26 rue d'Ulm, 75248 Paris Cedex 05, France. Tel.: 33 1 42 34 67 01. Fax: 33 1 46 33 30 16. email: almouzni{at}curie.fr

Heterochromatin is thought to play a critical role for centromeric function. However, the respective contributions of the distinct repetitive sequences found in these regions, such as minor and major satellites in the mouse, have remained largely unsolved. We show that these centric and pericentric repeats on the chromosomes have distinct heterochromatic characteristics in the nucleus. Major satellites from different chromosomes form clusters associated with heterochromatin protein 1{alpha}, whereas minor satellites are individual entities associated with centromeric proteins. Both regions contain methylated histone H3 (Me-K9 H3) but show different micrococcal nuclease sensitivities. A dinucleosome repeating unit is found specifically associated with major satellites. These domains replicate asynchronously, and chromatid cohesion is sustained for a longer time in major satellites compared with minor satellites. Such prolonged cohesion in major satellites is lost in the absence of Suv39h histone methyltransferases. Thus, we define functionally independent centromeric subdomains, which spatio-temporal isolation is proposed to be important for centromeric cohesion and dissociation during chromosome segregation.

Key Words: centromere; cohesion; replication; nuclear organization; cluster


Abbreviations used in this paper: ACA, anticentromere antibody; BiodU, Biotin-16-deoxyuridine; CENP, centromeric protein; di-Me-K9 H3, histone H3 di-methylated at lysine 9; dn, double null; HP1, heterochromatin protein 1; Me-K9 H3, histone H3 methylated at lysine 9; Mnase, micrococcal nuclease; mono-Me-K9 H3, histone H3 mono-methylated at lysine 9; NChIP, native chromatin immunoprecipitation; tri-Me-K9 H3, histone H3 tri-methylated at lysine 9.


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