Browse
Submit Data
Databases
API
Help

Dataset Information

0 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 | 2016 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

The molecular basis for centromere identity and function.

McKinley Kara L KL Cheeseman Iain M IM

Nature reviews. Molecular cell biology 20151125 1

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 ...[more]

PMID: 26601620

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

EWSR1 maintains centromere identity.

Project description:The centromere is essential for ensuring high-fidelity transmission of chromosomes. CENP-A, the centromeric histone H3 variant, is thought to be the epigenetic mark of centromere identity. CENP-A deposition at the centromere is crucial for proper centromere function and inheritance. Despite its importance, the precise mechanism responsible for maintenance of centromere position remains obscure. Here, we report a mechanism to maintain centromere identity. We demonstrate that CENP-A interacts with EWSR1 (Ewing sarcoma breakpoint region 1) and EWSR1-FLI1 (the oncogenic fusion protein in Ewing sarcoma). EWSR1 is required for maintaining CENP-A at the centromere in interphase cells. EWSR1 and EWSR1-FLI1 bind CENP-A through the SYGQ2 region within the prion-like domain, important for phase separation. EWSR1 binds to R-loops through its RNA-recognition motif in vitro. Both the domain and motif are required for maintaining CENP-A at the centromere. Therefore, we conclude that EWSR1 guards CENP-A in centromeric chromatins by binding to centromeric RNA.

| S-EPMC10758295 | 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

Reconstituting Drosophila Centromere Identity in Human Cells.

Project description:The centromere is an essential chromosomal region required for accurate chromosome segregation. Most eukaryotic centromeres are defined epigenetically by the histone H3 variant, centromere protein (CENP)-A, yet how its self-propagation is achieved remains poorly understood. Here, we develop a heterologous system to reconstitute epigenetic inheritance of centromeric chromatin by ectopically targeting the Drosophila centromere proteins dCENP-A, dCENP-C, and CAL1 to LacO arrays in human cells. Dissecting the function of these three components uncovers the key role of self-association of dCENP-C and CAL1 for their mutual interaction and dCENP-A deposition. Importantly, we identify CAL1 to be required for dCENP-C loading onto chromatin in cooperation with dCENP-A nucleosomes, thus closing the epigenetic loop to ensure dCENP-C and dCENP-A replenishment during the cell division cycle. Finally, we show that all three factors are sufficient for dCENP-A propagation and propose a model for the epigenetic inheritance of Drosophila centromere identity.

| S-EPMC6900781 | 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

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

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