Posttranslational modifications of CENP-A: marks of distinction

Srivastava, Shashank; Foltz, Daniel R.

doi:10.1007/s00412-018-0665-x

Cited by 43 publications

(36 citation statements)

References 120 publications

(183 reference statements)

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“…It contributes to the interactions with the kinetochore proteins CENP-B, CENP-C and CENP-T [51,52,56,57], although there may be species-specific differences in how these proteins interact. Different post-translational modifications (PTMs) on the CENP-A N-terminal tail have also been described to affect centromere establishment and maintenance [53,54,58–63].…”

Section: Discussionmentioning

confidence: 99%

Trans-generational inheritance of centromere identity requires the CENP-A N-terminal tail in theC. elegansmaternal germ line

Prosee

Wenda

Gabus

et al. 2020

Preprint

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Centromere protein A (CENP-A) is a histone H3 variant that defines centromeric chromatin and is essential for centromere function. In most eukaryotes CENP-A-containing chromatin is epigenetically maintained, and centromere identity is inherited from one cell cycle to the next. In the germ line of the holocentric nematode Caenorhabditis elegans, this inheritance cycle is disrupted. CENP-A is removed at the mitosis-to-meiosis transition and is established de novo on chromatin during diplotene of meiosis I. Here we show that the N-terminal tail of CENP-A is required for the de novo establishment of centromeres, but dispensable for centromere maintenance during embryogenesis. Worms homozygous for a CENP-A tail deletion maintain a functional centromere during development, but give rise to inviable offspring because they fail to re-establish centromeres in the maternal germ line. We identify the N-terminal tail of CENP-A as a critical domain for the interaction with the conserved kinetochore protein KNL-2, and argue that this interaction plays an important role in setting centromere identity in the germ line. We conclude that centromere establishment and maintenance are functionally distinct in C. elegans.

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Section: Discussionmentioning

confidence: 99%

Trans-generational inheritance of centromere identity requires the CENP-A N-terminal tail in theC. elegansmaternal germ line

Prosee

Wenda

Gabus

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…This is due to, inter alia , the lower lysine content in CENP-A . In histone H3, up to 17 different types of post-translational modifications were found ( Xu et al 2014 ), whereas only four modifications were detected in CENP-A : methylation, acetylation, phosphorylation and ubiquitination ( Srivastava and Foltz 2018 ). The most characteristic CENP-A modifications are Gly1 trimethylation, Ser 7, 16, 18 and 68 phosphorylation and monomethylation, acetylation and ubiquitination of lysine 124.…”

Section: Epigenetic Regulation Of Centromeres and Pericentromeresmentioning

confidence: 99%

“…The most characteristic CENP-A modifications are Gly1 trimethylation, Ser 7, 16, 18 and 68 phosphorylation and monomethylation, acetylation and ubiquitination of lysine 124. These CENP-A -specific modifications, play an important role in chromosome segregation during cell division, because they regulate CENP-A deposition in centromeric chromatin and participate in CCAN recruitment ( Srivastava and Foltz 2018 ).…”

Section: Epigenetic Regulation Of Centromeres and Pericentromeresmentioning

confidence: 99%

The epigenetic regulation of centromeres and telomeres in plants and animals

Achrem

Szućko

Kalinka

2020

CCG

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The centromere is a chromosomal region where the kinetochore is formed, which is the attachment point of spindle fibers. Thus, it is responsible for the correct chromosome segregation during cell division. Telomeres protect chromosome ends against enzymatic degradation and fusions, and localize chromosomes in the cell nucleus. For this reason, centromeres and telomeres are parts of each linear chromosome that are necessary for their proper functioning. More and more research results show that the identity and functions of these chromosomal regions are epigenetically determined. Telomeres and centromeres are both usually described as highly condensed heterochromatin regions. However, the epigenetic nature of centromeres and telomeres is unique, as epigenetic modifications characteristic of both eu- and heterochromatin have been found in these areas. This specificity allows for the proper functioning of both regions, thereby affecting chromosome homeostasis. This review focuses on demonstrating the role of epigenetic mechanisms in the functioning of centromeres and telomeres in plants and animals.

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“…Despite this, chromosome segregation might be compromised due to the specific loss of old nucleosomes with specific PTMs. PTMs relevant for centromere function have been identified on CENP-A and shown to affect CENP-A stability and correct mitotic progression 65,66 . Moreover, methylation of lysine 20 on the associated H4 plays an essential role for kinetochore formation 67 .…”

Section: Discussionmentioning

confidence: 99%

Spt6 is a maintenance factor for centromeric CENP-A

et al. 2020

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Replication and transcription of genomic DNA requires partial disassembly of nucleosomes to allow progression of polymerases. This presents both an opportunity to remodel the underlying chromatin and a danger of losing epigenetic information. Centromeric transcription is required for stable incorporation of the centromere-specific histone dCENP-A in M/G1 phase, which depends on the eviction of previously deposited H3/H3.3-placeholder nucleosomes. Here we demonstrate that the histone chaperone and transcription elongation factor Spt6 spatially and temporarily coincides with centromeric transcription and prevents the loss of old CENP-A nucleosomes in both Drosophila and human cells. Spt6 binds directly to dCENP-A and dCENP-A mutants carrying phosphomimetic residues alleviate this association. Retention of phosphomimetic dCENP-A mutants is reduced relative to wildtype, while non-phosphorylatable dCENP-A retention is increased and accumulates at the centromere. We conclude that Spt6 acts as a conserved CENP-A maintenance factor that ensures longterm stability of epigenetic centromere identity during transcription-mediated chromatin remodeling.

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Posttranslational modifications of CENP-A: marks of distinction

Cited by 43 publications

References 120 publications

Trans-generational inheritance of centromere identity requires the CENP-A N-terminal tail in theC. elegansmaternal germ line

Trans-generational inheritance of centromere identity requires the CENP-A N-terminal tail in theC. elegansmaternal germ line

The epigenetic regulation of centromeres and telomeres in plants and animals

Spt6 is a maintenance factor for centromeric CENP-A

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