Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The molecular basis for centromere identity and function.

ABSTRACT: The centromere is the region of the chromosome that directs its segregation in mitosis and meiosis. Although the functional importance of the centromere has been appreciated for more than 130 years, elucidating the molecular features and properties that enable centromeres to orchestrate chromosome segregation is an ongoing challenge. Most eukaryotic centromeres are defined epigenetically and require the presence of nucleosomes containing the histone H3 variant centromere protein A (CENP-A; also known as CENH3). Ongoing work is providing important molecular insights into the central requirements for centromere identity and propagation, and the mechanisms by which centromeres recruit kinetochores to connect to spindle microtubules.

SUBMITTER: McKinley KL

PROVIDER: S-EPMC8603311 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Molecular underpinnings of centromere identity and maintenance.

Project description:Centromeres direct faithful chromosome inheritance at cell division but are not defined by a conserved DNA sequence. Instead, a specialized form of chromatin containing the histone H3 variant, CENP-A, epigenetically specifies centromere location. We discuss current models where CENP-A serves as the marker for the centromere during the entire cell cycle in addition to generating the foundational chromatin for the kinetochore in mitosis. Recent elegant experiments have indicated that engineered arrays of CENP-A-containing nucleosomes are sufficient to serve as the site of kinetochore formation and for seeding centromeric chromatin that self-propagates through cell generations. Finally, recent structural and dynamic studies of CENP-A-containing histone complexes - before and after assembly into nucleosomes - provide models to explain underlying molecular mechanisms at the centromere.

| S-EPMC3614489 | biostudies-literature

Centromere identity, function, and epigenetic propagation across cell divisions.

Project description:The key to understanding centromere identity is likely to lie in the chromatin containing the histone H3 variant CENP-A. CENP-A is the prime candidate to carry the epigenetic information that specifies the chromosomal location of the centromere in nearly all eukaryotic species, raising questions fundamental to understanding chromosome inheritance: How is the epigenetic centromere mark propagated? What physical properties of CENP-A-containing complexes are important for epigenetically marking centromeres? What are the molecules that recognize centromeric chromatin and serve as the foundation for the mitotic kinetochore? We discuss recent advances from our research groups that have yielded substantial insight into these questions and present our current understanding of the centromere. Future work promises an understanding of the molecular processes that confer fidelity to genome transmission at cell division.

| S-EPMC3140419 | biostudies-literature

A two-step mechanism for epigenetic specification of centromere identity and function.

Project description:The basic determinant of chromosome inheritance, the centromere, is specified in many eukaryotes by an epigenetic mark. Using gene targeting in human cells and fission yeast, chromatin containing the centromere-specific histone H3 variant CENP-A is demonstrated to be the epigenetic mark that acts through a two-step mechanism to identify, maintain and propagate centromere function indefinitely. Initially, centromere position is replicated and maintained by chromatin assembled with the centromere-targeting domain (CATD) of CENP-A substituted into H3. Subsequently, nucleation of kinetochore assembly onto CATD-containing chromatin is shown to require either the amino- or carboxy-terminal tail of CENP-A for recruitment of inner kinetochore proteins, including stabilizing CENP-B binding to human centromeres or direct recruitment of CENP-C, respectively.

| S-EPMC4418506 | biostudies-literature

Molecular Basis for CPC-Sgo1 Interaction: Implications for Centromere Localisation and Function of the CPCMolecular Basis for CPC-Sgo1 Interaction: Implications for Centromere Localisation and Function of the CPC

Project description:Sgo1 makes multipartite interactions with CPC subunits Previous studies have suggested that the Sgo1-CPC (Chromosomal Passenger Complex) interaction is mediated via the N-terminal coiled-coil of Sgo1 and Borealin. However, our structural data revealed that the very N-terminus of Sgo1 can interact with the BIR domain of Survivin. Together, these studies suggest that multi-partite interactions between Sgo1 and different CPC subunits could facilitate CPC-Sgo1 complex formation. To gain further structural insights, we performed chemical cross-linking of the CPCISB10-280-Sgo11-415 complex using a zero-length cross-linker, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), followed by mass spectrometry analysis. Cross-linking-mass spectrometry (CLMS) data showed that: (1) consistent with our previous observations, the N-terminal region of Sgo1 (amino acids 1-34) makes extensive contacts with Survivin BIR domain (amino acids 18-89); (2) the N-terminal coiled-coil of Sgo1 (amino acids 10-120) interacts with the CPC triple helical bundle; (3) consistent with previous findings, the N-terminal coiled-coil also contacts the Borealin dimerisation domain; and (4) the Sgo1 region beyond the N-terminal coil-coil region, which is predicted to be unstructured, contacts both Survivin and Borealin with most contacts confined to the Sgo1 central region spanning amino acids (aa) 180-300. Thus, our cross-linking results suggests that Sgo1 interacts with CPC, mainly via two regions, the N-terminal coiled-coil domain and the unstructured central region.

2022-06-29 | PXD028433 | Pride

Mechanistic basis for Sgo1-mediated centromere localization and function of the CPC.

Project description:Centromere association of the chromosomal passenger complex (CPC; Borealin-Survivin-INCENP-Aurora B) and Sgo1 is crucial for chromosome biorientation, a process essential for error-free chromosome segregation. Phosphorylated histone H3 Thr3 (H3T3ph; directly recognized by Survivin) and histone H2A Thr120 (H2AT120ph; indirectly recognized via Sgo1), together with CPC's intrinsic nucleosome-binding ability, facilitate CPC centromere recruitment. However, the molecular basis for CPC-Sgo1 binding and how their physical interaction influences CPC centromere localization are lacking. Here, using an integrative structure-function approach, we show that the "histone H3-like" Sgo1 N-terminal tail-Survivin BIR domain interaction acts as a hotspot essential for CPC-Sgo1 assembly, while downstream Sgo1 residues and Borealin contribute for high-affinity binding. Disrupting Sgo1-Survivin interaction abolished CPC-Sgo1 assembly and perturbed CPC centromere localization and function. Our findings reveal that Sgo1 and H3T3ph use the same surface on Survivin to bind CPC. Hence, it is likely that these interactions take place in a spatiotemporally restricted manner, providing a rationale for the Sgo1-mediated "kinetochore-proximal" CPC centromere pool.

| S-EPMC9253516 | biostudies-literature

Establishment of centromere identity is dependent on nuclear spatial organization.

Project description:The establishment of centromere-specific CENP-A chromatin is influenced by epigenetic and genetic processes. Central domain sequences from fission yeast centromeres are preferred substrates for CENP-ACnp1 incorporation, but their use is context dependent, requiring adjacent heterochromatin. CENP-ACnp1 overexpression bypasses heterochromatin dependency, suggesting that heterochromatin ensures exposure to conditions or locations permissive for CENP-ACnp1 assembly. Centromeres cluster around spindle-pole bodies (SPBs). We show that heterochromatin-bearing minichromosomes localize close to SPBs, consistent with this location promoting CENP-ACnp1 incorporation. We demonstrate that heterochromatin-independent de novo CENP-ACnp1 chromatin assembly occurs when central domain DNA is placed near, but not far from, endogenous centromeres or neocentromeres. Moreover, direct tethering of central domain DNA at SPBs permits CENP-ACnp1 assembly, suggesting that the nuclear compartment surrounding SPBs is permissive for CENP-ACnp1 incorporation because target sequences are exposed to high levels of CENP-ACnp1 and associated assembly factors. Thus, nuclear spatial organization is a key epigenetic factor that influences centromere identity.

| S-EPMC9616734 | biostudies-literature

Structural Basis for CAL1-Mediated Centromere Maintenance

Project description:Intermolecular interactions stabilising the CAL1–CENP-A/H4 complex were analysed using chemical Cross-Linking Mass Spectrometry (CLMS). Purified recombinant CAL11-160–CENP-A101-225–H4 complex was crosslinked using EDC and BS3. The crosslinked peptides were analysed by mass spectrometry to identify intra- and intermolecular contacts. Notably, the data revealed several intramolecular crosslinks between the N- and C-terminal regions of CAL11-160, suggesting a direct interaction between these regions.

2020-03-11 | PXD017238 | Pride

CENP-A: the key player behind centromere identity, propagation, and kinetochore assembly.

Project description:Chromosome segregation is the one of the great problems in biology with complexities spanning from biophysics and polymer dynamics to epigenetics. Here, we summarize the current knowledge and highlight gaps in understanding of the mechanisms controlling epigenetic regulation of chromosome segregation.

| S-EPMC3501172 | biostudies-literature

Centromere identity is specified by a single centromeric nucleosome in budding yeast.

Project description:Chromosome segregation ensures that DNA is equally divided between daughter cells during each round of cell division. The centromere (CEN) is the specific locus on each chromosome that directs formation of the kinetochore, the multiprotein complex that interacts with the spindle microtubules to promote proper chromosomal alignment and segregation during mitosis. CENs are organized into a specialized chromatin structure due to the incorporation of an essential CEN-specific histone H3 variant (CenH3) in the centromeric nucleosomes of all eukaryotes. Consistent with its essential role at the CEN, the loss or up-regulation of CenH3 results in mitotic defects. Despite the requirement for CenH3 in CEN function, it is unclear how CenH3 nucleosomes structurally organize centromeric DNA to promote formation of the kinetochore. To address this issue, we developed a modified chromatin immunoprecipitation approach to analyze the number and position of CenH3 nucleosomes at the budding yeast CEN. Using this technique, we show that yeast CENs have a single CenH3 nucleosome positioned over the CEN-determining elements. Therefore, a single CenH3 nucleosome forms the minimal unit of centromeric chromatin necessary for kinetochore assembly and proper chromosome segregation.

| S-EPMC1976213 | biostudies-literature

Histone-histone interactions and centromere function.

Project description:Cse4p is a structural component of the core centromere of Saccharomyces cerevisiae and is a member of the conserved CENP-A family of specialized histone H3 variants. The histone H4 allele hhf1-20 confers defects in core centromere chromatin structure and mitotic chromosome transmission. We have proposed that Cse4p and histone H4 interact through their respective histone fold domains to assemble a nucleosome-like structure at centromeric DNA. To test this model, we targeted random mutations to the Cse4p histone fold domain and isolated three temperature-sensitive cse4 alleles in an unbiased genetic screen. Two of the cse4 alleles contain mutations at the Cse4p-H4 interface. One of these requires two widely separated mutations demonstrating long-range cooperative interactions in the structure. The third cse4 allele is mutated at its helix 2-helix 3 interface, a region required for homotypic H3 fold dimerization. Overexpression of wild-type Cse4p and histone H4 confer reciprocal allele-specific suppression of cse4 and hhf1 mutations, providing strong evidence for Cse4p-H4 protein interaction. Overexpression of histone H3 is dosage lethal in cse4 mutants, suggesting that histone H3 competes with Cse4p for histone H4 binding. However, the relative resistance of the Cse4p-H4 pathway to H3 interference argues that centromere chromatin assembly must be highly regulated.

| S-EPMC86044 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data