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Focus on the centre: the role of chromatin on the regulation of centromere identity and function.

Torras-Llort M, Moreno-Moreno O, Azorín F - EMBO J. (2009)

Bottom Line: Nowadays, we know that centromere identity is determined epigenetically by the formation of a unique type of chromatin, which is characterised by the presence of the centromere-specific histone H3 variant CenH3, originally called CENP-A, which replaces canonical histone H3 at centromeres.CenH3-chromatin constitutes the physical and functional foundation for kinetochore assembly.This review explores recent studies addressing the structural and functional characterisation of CenH3-chromatin, its assembly and propagation during mitosis, and its contribution to kinetochore assembly.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Biology of Barcelona, CSIC, and Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain.

ABSTRACT
The centromere is a specialised chromosomal structure that regulates faithful chromosome segregation during cell division, as it dictates the site of assembly of the kinetochore, a critical structure that mediates binding of chromosomes to the spindle, monitors bipolar attachment and pulls chromosomes to the poles during anaphase. Identified more than a century ago as the primary constriction of condensed metaphase chromosomes, the centromere remained elusive to molecular characterisation for many years owed to its unusual enrichment in highly repetitive satellite DNA sequences, except in budding yeast. In the last decade, our understanding of centromere structure, organisation and function has increased tremendously. Nowadays, we know that centromere identity is determined epigenetically by the formation of a unique type of chromatin, which is characterised by the presence of the centromere-specific histone H3 variant CenH3, originally called CENP-A, which replaces canonical histone H3 at centromeres. CenH3-chromatin constitutes the physical and functional foundation for kinetochore assembly. This review explores recent studies addressing the structural and functional characterisation of CenH3-chromatin, its assembly and propagation during mitosis, and its contribution to kinetochore assembly.

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Assembly and dynamic behaviour of CenH3-chromatin during cell cycle. Like other histone variants, CenH3 incorporates into chromatin independently of DNA replication. Deposition of newly synthesised CenH3 takes place during mitosis, at late telophase, or early G1. Specific CenH3 chaperones localise to the centromere coincidentally with deposition of new CenH3 and mediate assembly of CenH3-nucleosomes. During assembly, CenH3 might become resistant to proteolysis that, otherwise, degrades CenH3 and prevents deposition at non-centromeric sites. Before deposition, at late anaphase, specific complexes (Mis16/Mis18) seem to modify centromeric chromatin to allow assembly of new CenH3-nucleosomes. During DNA replication at S-phase, CenH3 concentration at centromeres is diluted and kinetochore assembly takes place before replenishment with new CenH3-nucleosomes. It is unclear whether ‘gaps' generated during DNA replication remain nucleosome-free or are filled by replicative H3-nucleosomes. It might also be possible that CenH3-nucleosomes are disassembled into ‘half-nucleosomes' to compensate for this deficit.
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f4: Assembly and dynamic behaviour of CenH3-chromatin during cell cycle. Like other histone variants, CenH3 incorporates into chromatin independently of DNA replication. Deposition of newly synthesised CenH3 takes place during mitosis, at late telophase, or early G1. Specific CenH3 chaperones localise to the centromere coincidentally with deposition of new CenH3 and mediate assembly of CenH3-nucleosomes. During assembly, CenH3 might become resistant to proteolysis that, otherwise, degrades CenH3 and prevents deposition at non-centromeric sites. Before deposition, at late anaphase, specific complexes (Mis16/Mis18) seem to modify centromeric chromatin to allow assembly of new CenH3-nucleosomes. During DNA replication at S-phase, CenH3 concentration at centromeres is diluted and kinetochore assembly takes place before replenishment with new CenH3-nucleosomes. It is unclear whether ‘gaps' generated during DNA replication remain nucleosome-free or are filled by replicative H3-nucleosomes. It might also be possible that CenH3-nucleosomes are disassembled into ‘half-nucleosomes' to compensate for this deficit.

Mentions: Contrary to canonical histones, which are deposited during DNA replication, CenH3 incorporates into chromatin independently of DNA replication, similar to other histone variants (Shelby et al, 2000; Ahmad and Henikoff, 2001) (Figure 4). In human cells, CenH3CENP-A levels peak in G2 (Shelby et al, 1997, 2000), and deposition of new CenH3CENP-A occurs during mitosis, at late telophase, and early G1 (Jansen et al, 2007; Hemmerich et al, 2008). In syncytial Drosophila embryos, in which no G1/G2-phases are observed, CenH3CID deposition also takes place during mitosis, at anaphase (Schuh et al, 2007). Yeasts constitute an exception to this rule as, in S. cerevisiae, all pre-existing CenH3Cse4 is evicted from centromeres and replaced by newly synthesised CenH3Cse4 during S-phase (Pearson et al, 2004) whereas, in S. pombe, in which G1-phase is exceedingly short, CenH3Cnp1 deposition takes place in two phases, during S and in late G2 (Takayama et al, 2008). In Arabidopsis, it was reported that loading of CenH3 also occurs mainly in G2 (Lermontova et al, 2006). As a consequence of its loading outside of S-phase, CenH3 concentration at centromeres is diluted during DNA replication, generating ‘gaps' that could remain nucleosome-free, ready for CenH3 deposition during mitosis, or be filled by replicative H3-nucleosomes that, later, would be replaced by CenH3-nucleosomes (Figure 4). It might also be possible that, during DNA replication, CenH3-nucleosomes are disassembled into heterotypic tetramers or ‘half-nucleosomes'.


Focus on the centre: the role of chromatin on the regulation of centromere identity and function.

Torras-Llort M, Moreno-Moreno O, Azorín F - EMBO J. (2009)

Assembly and dynamic behaviour of CenH3-chromatin during cell cycle. Like other histone variants, CenH3 incorporates into chromatin independently of DNA replication. Deposition of newly synthesised CenH3 takes place during mitosis, at late telophase, or early G1. Specific CenH3 chaperones localise to the centromere coincidentally with deposition of new CenH3 and mediate assembly of CenH3-nucleosomes. During assembly, CenH3 might become resistant to proteolysis that, otherwise, degrades CenH3 and prevents deposition at non-centromeric sites. Before deposition, at late anaphase, specific complexes (Mis16/Mis18) seem to modify centromeric chromatin to allow assembly of new CenH3-nucleosomes. During DNA replication at S-phase, CenH3 concentration at centromeres is diluted and kinetochore assembly takes place before replenishment with new CenH3-nucleosomes. It is unclear whether ‘gaps' generated during DNA replication remain nucleosome-free or are filled by replicative H3-nucleosomes. It might also be possible that CenH3-nucleosomes are disassembled into ‘half-nucleosomes' to compensate for this deficit.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2722248&req=5

f4: Assembly and dynamic behaviour of CenH3-chromatin during cell cycle. Like other histone variants, CenH3 incorporates into chromatin independently of DNA replication. Deposition of newly synthesised CenH3 takes place during mitosis, at late telophase, or early G1. Specific CenH3 chaperones localise to the centromere coincidentally with deposition of new CenH3 and mediate assembly of CenH3-nucleosomes. During assembly, CenH3 might become resistant to proteolysis that, otherwise, degrades CenH3 and prevents deposition at non-centromeric sites. Before deposition, at late anaphase, specific complexes (Mis16/Mis18) seem to modify centromeric chromatin to allow assembly of new CenH3-nucleosomes. During DNA replication at S-phase, CenH3 concentration at centromeres is diluted and kinetochore assembly takes place before replenishment with new CenH3-nucleosomes. It is unclear whether ‘gaps' generated during DNA replication remain nucleosome-free or are filled by replicative H3-nucleosomes. It might also be possible that CenH3-nucleosomes are disassembled into ‘half-nucleosomes' to compensate for this deficit.
Mentions: Contrary to canonical histones, which are deposited during DNA replication, CenH3 incorporates into chromatin independently of DNA replication, similar to other histone variants (Shelby et al, 2000; Ahmad and Henikoff, 2001) (Figure 4). In human cells, CenH3CENP-A levels peak in G2 (Shelby et al, 1997, 2000), and deposition of new CenH3CENP-A occurs during mitosis, at late telophase, and early G1 (Jansen et al, 2007; Hemmerich et al, 2008). In syncytial Drosophila embryos, in which no G1/G2-phases are observed, CenH3CID deposition also takes place during mitosis, at anaphase (Schuh et al, 2007). Yeasts constitute an exception to this rule as, in S. cerevisiae, all pre-existing CenH3Cse4 is evicted from centromeres and replaced by newly synthesised CenH3Cse4 during S-phase (Pearson et al, 2004) whereas, in S. pombe, in which G1-phase is exceedingly short, CenH3Cnp1 deposition takes place in two phases, during S and in late G2 (Takayama et al, 2008). In Arabidopsis, it was reported that loading of CenH3 also occurs mainly in G2 (Lermontova et al, 2006). As a consequence of its loading outside of S-phase, CenH3 concentration at centromeres is diluted during DNA replication, generating ‘gaps' that could remain nucleosome-free, ready for CenH3 deposition during mitosis, or be filled by replicative H3-nucleosomes that, later, would be replaced by CenH3-nucleosomes (Figure 4). It might also be possible that, during DNA replication, CenH3-nucleosomes are disassembled into heterotypic tetramers or ‘half-nucleosomes'.

Bottom Line: Nowadays, we know that centromere identity is determined epigenetically by the formation of a unique type of chromatin, which is characterised by the presence of the centromere-specific histone H3 variant CenH3, originally called CENP-A, which replaces canonical histone H3 at centromeres.CenH3-chromatin constitutes the physical and functional foundation for kinetochore assembly.This review explores recent studies addressing the structural and functional characterisation of CenH3-chromatin, its assembly and propagation during mitosis, and its contribution to kinetochore assembly.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Biology of Barcelona, CSIC, and Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain.

ABSTRACT
The centromere is a specialised chromosomal structure that regulates faithful chromosome segregation during cell division, as it dictates the site of assembly of the kinetochore, a critical structure that mediates binding of chromosomes to the spindle, monitors bipolar attachment and pulls chromosomes to the poles during anaphase. Identified more than a century ago as the primary constriction of condensed metaphase chromosomes, the centromere remained elusive to molecular characterisation for many years owed to its unusual enrichment in highly repetitive satellite DNA sequences, except in budding yeast. In the last decade, our understanding of centromere structure, organisation and function has increased tremendously. Nowadays, we know that centromere identity is determined epigenetically by the formation of a unique type of chromatin, which is characterised by the presence of the centromere-specific histone H3 variant CenH3, originally called CENP-A, which replaces canonical histone H3 at centromeres. CenH3-chromatin constitutes the physical and functional foundation for kinetochore assembly. This review explores recent studies addressing the structural and functional characterisation of CenH3-chromatin, its assembly and propagation during mitosis, and its contribution to kinetochore assembly.

Show MeSH
Related in: MedlinePlus