Mutation and selection explain why eukaryotic centromeric DNA is often A+T rich
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ABSTRACT:
PROVIDER: PRJNA753506 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15406602_1.fastq.gz | Fastqsanger.gz | |||
| SRR15406602_2.fastq.gz | Fastqsanger.gz | |||
| SRR15406603_1.fastq.gz | Fastqsanger.gz | |||
| SRR15406603_2.fastq.gz | Fastqsanger.gz | |||
| SRR15406604_1.fastq.gz | Fastqsanger.gz |
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Project description:The reasons why centromeric DNA is often A+T rich are not understood. We have used chromosome engineering to replace native centromeric DNA with different test sequences at native centromeres in two different strains of the fission yeast Schizosaccharomyces pombe and have discovered that A+T rich DNA, whether synthetic or of bacterial origin, will function as a centromere and that the functionality of the A+T rich DNA does not differ substantially from that of native centromeric DNA. Using genome size as a surrogate for the inverse of effective population size (Ne) we also show that the relative A+T content of centromeric DNA scales with Ne across 45 eukaryotic species. This suggests that in most eukaryotes the A+T content of the centromeric DNA is adaptive and that the A+T content of centromeric DNA is determined by a balance between selection and mutation. Combing the experimental results and the evolutionary analyses allows us to conclude that A+T rich DNA of almost any sequence will function as a centromere in most eukaryotes. The fact that many G/C to A/T substitutions are unlikely to be selected against may contribute to the rapid evolution of centromeric DNA. We also show that neo-centromeres are not simply weak versions of native centromeres but that their establishment or inheritance may require factors in addition to those required by native centromeres.
2021-11-26 | GSE181806 | GEO
Project description:We have used chromosome engineering to replace native centromeric DNA with different test sequences at native centromeres in two different strains of the fission yeast Schizosaccharomyces pombe and have discovered that A + T rich DNA, whether synthetic or of bacterial origin, will function as a centromere in this species. Using genome size as a surrogate for the inverse of effective population size (Ne) we also show that the relative A + T content of centromeric DNA scales with Ne across 43 animal, fungal and yeast (Opisthokonta) species. This suggests that in most of these species the A + T content of the centromeric DNA is determined by a balance between selection and mutation. Combining the experimental results and the evolutionary analyses allows us to conclude that A + T rich DNA of almost any sequence will function as a centromere in most Opisthokonta species. The fact that many G/C to A/T substitutions are unlikely to be selected against may contribute to the rapid evolution of centromeric DNA. We also show that a neo-centromere sequence is not simply a weak version of native centromeric DNA and suggest that neo-centromeres require factors either for their propagation or establishment in addition to those required by native centromeres.
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Project description:In human cells chromosome specific aneuploidy was measured. Then, using NGS methods, centromeric features were measured for each chromosome (including centromere length and amount of centromeric proteins). The study aims at testing an association between centromeric features and missegregation rate.
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Project description:Centromeres are the regions of eukaryotic chromosomes where kinetochores are assembled and direct the correct segregation of chromosomes. Active centromeres are defined by presence of nucleosomes containing CENP-A, a histone H3 variant, which alone is sufficient to direct kinetochore assembly. Once assembled at a location CENP-A chromatin and the kinetochore is maintained at that location though a positive feedback loop where kinetochore proteins recruited by CENP-A promote deposition of new CENP-A following replication. Although CENP-A chromatin itself is a heritable entity, it is normally associated with specific sequences such as human alpha satellite arrays. Such analyses suggest that properties of centromeric DNA itself may favour assembly of CENP-A rather than H3 nucleosomes. To investigate the innate properties of centromeric DNA we have examined histone dynamics on this DNA assembled in CENP-A chromatin at endogenous centromeres and when assembled only in H3 chromatin at an ectopic location. We demonstrate that H3 occupancy on centromeric DNA is innately low while H3 turnover is high. Moreover, even at an ectopic location centromeric DNA programs H3 deposition in S phase and its eviction during G2 when CENP-A is otherwise deposited. G2 accumulation of RNAPII on centromeric DNA during G2 is consistent with transcription-coupled destabilisation of H3 nucleosomes to favour CENP-A deposition.
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Project description:Centromeres are the regions of eukaryotic chromosomes where kinetochores are assembled and direct the correct segregation of chromosomes. Active centromeres are defined by presence of nucleosomes containing CENP-A, a histone H3 variant, which alone is sufficient to direct kinetochore assembly. Once assembled at a location CENP-A chromatin and the kinetochore is maintained at that location though a positive feedback loop where kinetochore proteins recruited by CENP-A promote deposition of new CENP-A following replication. Although CENP-A chromatin itself is a heritable entity, it is normally associated with specific sequences such as human alpha satellite arrays. Such analyses suggest that properties of centromeric DNA itself may favour assembly of CENP-A rather than H3 nucleosomes. To investigate the innate properties of centromeric DNA we have examined histone dynamics on this DNA assembled in CENP-A chromatin at endogenous centromeres and when assembled only in H3 chromatin at an ectopic location. We demonstrate that H3 occupancy on centromeric DNA is innately low while H3 turnover is high. Moreover, even at an ectopic location centromeric DNA programs H3 deposition in S phase and its eviction during G2 when CENP-A is otherwise deposited. G2 accumulation of RNAPII on centromeric DNA during G2 is consistent with transcription-coupled destabilisation of H3 nucleosomes to favour CENP-A deposition.
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Project description:Centromeres are the regions of eukaryotic chromosomes where kinetochores are assembled and direct the correct segregation of chromosomes. Active centromeres are defined by presence of nucleosomes containing CENP-A, a histone H3 variant, which alone is sufficient to direct kinetochore assembly. Once assembled at a location CENP-A chromatin and the kinetochore is maintained at that location though a positive feedback loop where kinetochore proteins recruited by CENP-A promote deposition of new CENP-A following replication. Although CENP-A chromatin itself is a heritable entity, it is normally associated with specific sequences such as human alpha satellite arrays. Such analyses suggest that properties of centromeric DNA itself may favour assembly of CENP-A rather than H3 nucleosomes. To investigate the innate properties of centromeric DNA we have examined histone dynamics on this DNA assembled in CENP-A chromatin at endogenous centromeres and when assembled only in H3 chromatin at an ectopic location. We demonstrate that H3 occupancy on centromeric DNA is innately low while H3 turnover is high. Moreover, even at an ectopic location centromeric DNA programs H3 deposition in S phase and its eviction during G2 when CENP-A is otherwise deposited. G2 accumulation of RNAPII on centromeric DNA during G2 is consistent with transcription-coupled destabilisation of H3 nucleosomes to favour CENP-A deposition.
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Project description:Functional centromeres are essential for proper cell division. Centromeres are established largely by epigenetic processes resulting in incorporation of the histone H3 variant CENP-A. Here, we demonstrate the direct involvement of H2B monoubiquitination, mediated by RNF20 in humans or Brl1 in Schizosaccharomyces pombe, in centromeric chromatin maintenance. Monoubiquinated H2B (H2Bub1) is needed for this maintenance, promoting noncoding transcription, centromere integrity and accurate chromosomal segregation. A transient pulse of centromeric H2Bub1 leads to RNA polymerase II–mediated transcription of the centromere’s central domain, coupled to decreased H3 stability. H2Bub1-deficient cells have centromere cores that, despite their intact centromeric heterochromatin barriers, exhibit characteristics of heterochromatin, such as silencing histone modifications, reduced nucleosome turnover and reduced levels of transcription. In the H2Bub1-deficient cells, centromere functionality is hampered, thus resulting in unequal chromosome segregation. Therefore, centromeric H2Bub1 is essential for maintaining active centromeric chromatin.
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