Compartimentation et dynamique des fonctions nucléaires

Publications de l’équipe

Année de publication : 2018

Antoine Hocher, Myriam Ruault, Petra Kaferle, Marc Descrimes, Mickaël Garnier, Antonin Morillon, Angela Taddei (2018 Oct 26)

Expanding heterochromatin reveals discrete subtelomeric domains delimited by chromatin landscape transitions.

Genome research : DOI : gr.236554.118 En savoir plus

The eukaryotic genome is divided into chromosomal domains of heterochromatin and euchromatin. Transcriptionally silent heterochromatin is found at subtelomeric regions, leading to the telomeric position effect (TPE) in yeast fly and human. Heterochromatin generally initiates and spreads from defined loci, and diverse mechanisms prevent the ectopic spread of heterochromatin into euchromatin. Here, we overexpressed the silencing factor Sir3 at varying levels in yeast and found that Sir3 spreads into Extended Silent Domains (ESDs), eventually reaching saturation at subtelomeres. We observed the spread of Sir3 into subtelomeric domains associated with specific histone marks in wild-type cells and stopping at zones of histone mark transitions including H3K79 tri-methylation levels. Our study shows that the conserved H3K79 methyltransferase Dot1 is essential in restricting Sir3 spread beyond ESDs, thus ensuring viability upon overexpression of Sir3. Lastly, our analyses of published data demonstrate how ESDs unveil uncharacterized discrete domains isolating structural and functional subtelomeric features from the rest of the genome. Our work offers a new approach on how to separate subtelomeres from the core chromosome.


Année de publication : 2017

Amandine Batté, Clémentine Brocas, Hélène Bordelet, Antoine Hocher, Myriam Ruault, Adouda Adjiri, Angela Taddei, Karine Dubrana (2017 Jul 30)

Recombination at subtelomeres is regulated by physical distance, double-strand break resection and chromatin status.

The EMBO journal : 2609-2625 : DOI : 10.15252/embj.201796631 En savoir plus

Homologous recombination (HR) is a conserved mechanism that repairs broken chromosomes via intact homologous sequences. How different genomic, chromatin and subnuclear contexts influence HR efficiency and outcome is poorly understood. We developed an assay to assess HR outcome by gene conversion (GC) and break-induced replication (BIR), and discovered that subtelomeric double-stranded breaks (DSBs) are preferentially repaired by BIR despite the presence of flanking homologous sequences. Overexpression of a silencing-deficient SIR3 mutant led to active grouping of telomeres and specifically increased the GC efficiency between subtelomeres. Thus, physical distance limits GC at subtelomeres. However, the repair efficiency between reciprocal intrachromosomal and subtelomeric sequences varies up to 15-fold, depending on the location of the DSB, indicating that spatial proximity is not the only limiting factor for HR EXO1 deletion limited the resection at subtelomeric DSBs and improved GC efficiency. The presence of repressive chromatin at subtelomeric DSBs also favoured recombination, by counteracting EXO1-mediated resection. Thus, repressive chromatin promotes HR at subtelomeric DSBs by limiting DSB resection and protecting against genetic information loss.

Eldad Kepten, Judith Miné-Hattab (2017 Feb 28)

[Lamin A: a key protein in chromatin motion].

Medecine sciences : M/S : 126-130 : DOI : 10.1051/medsci/20173302004 En savoir plus


Année de publication : 2015

Ivaylo Nikolov, Angela Taddei (2015 Oct 30)

Linking replication stress with heterochromatin formation.

Chromosoma : 523-33 : DOI : 10.1007/s00412-015-0545-6 En savoir plus

The eukaryotic genome can be roughly divided into euchromatin and heterochromatin domains that are structurally and functionally distinct. Heterochromatin is characterized by its high compaction that impedes DNA transactions such as gene transcription, replication, or recombination. Beyond its role in regulating DNA accessibility, heterochromatin plays essential roles in nuclear architecture, chromosome segregation, and genome stability. The formation of heterochromatin involves special histone modifications and the recruitment and spreading of silencing complexes that impact the higher-order structures of chromatin; however, its molecular nature varies between different chromosomal regions and between species. Although heterochromatin has been extensively characterized, its formation and maintenance throughout the cell cycle are not yet fully understood. The biggest challenge for the faithful transmission of chromatin domains is the destabilization of chromatin structures followed by their reassembly on a novel DNA template during genomic replication. This destabilizing event also provides a window of opportunity for the de novo establishment of heterochromatin. In recent years, it has become clear that different types of obstacles such as tight protein-DNA complexes, highly transcribed genes, and secondary DNA structures could impede the normal progression of the replisome and thus have the potential to endanger the integrity of the genome. Multiple studies carried out in different model organisms have demonstrated the capacity of such replisome impediments to favor the formation of heterochromatin. Our review summarizes these reports and discusses the potential role of replication stress in the formation and maintenance of heterochromatin and the role that silencing proteins could play at sites where the integrity of the genome is compromised.