Conservative assembly and segregation of nucleosomal histories

Leffak, I.M.; Grainger, Robert M.; Weintraub, Harold

doi:10.1016/0092-8674(77)90282-3

Cited by 168 publications

(95 citation statements)

References 21 publications

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“…The organization of centromeric chromatin is essential not only for KT function during each round of mitosis but also for CEN propagation after each round of genome duplication. After DNA replication, existing histone octamers randomly distribute to each of the daughter strands, while newly synthesized histones fill in the gaps (17,18). Although such a passive mechanism may suffice for the propagation of CENs composed of large arrays of CenH3s, we have shown that yeast CENs contain only one Cse4 nucleosome.…”

Section: Discussionmentioning

confidence: 95%

“…Although such a passive mechanism may suffice for the propagation of CENs composed of large arrays of CenH3s, we have shown that yeast CENs contain only one Cse4 nucleosome. Assuming a conservative segregation of octamers, as it occurs throughout the genome (17,18), only one sister chromatid would inherit the old Cse4 nucleosome. In this case, CEN identity must be established by the de novo deposition of CenH3 every cell cycle on the other sister chromatid.…”

Section: Discussionmentioning

confidence: 99%

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

Furuyama

Biggins

2007

Proc. Natl. Acad. Sci. U.S.A.

240

216

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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 ͉ chromatin ͉ kinetochore C hromosome segregation is directed by the multiprotein kinetochore (KT) complex that assembles on centromeres (CENs) and interacts with the spindle apparatus to control chromosome movement during cell division (for reviews, see refs. 1 and 2). Although KT function is conserved, phylogenetic analysis of centromeric DNA reveals no common sequence element that would identify a CEN across species. Like all other parts of the genome, the DNA of CENs is organized into chromatin, a higher order structure in which DNA is wrapped around histones to generate nucleosomes. Typical octameric nucleosomes contain two molecules of each of four histones, H2A, H2B, H3, and H4, whereas centromeric nucleosomes are structurally distinct, containing an evolutionarily conserved CEN-specific histone H3 variant (CenH3) in place of canonical H3 (for review, see ref.3). The conservation of CenH3 across eukaryotes and its strict CEN localization in all species suggest that it is the epigenetic CEN identifier. Consistent with this finding, overexpression of the Drosophila CenH3 leads to its localization in euchromatin and the formation of ectopic KTs, resulting in subsequent defects in genomic stability (4).Despite the requirement for CenH3 in CEN specification, it is unclear how CenH3 nucleosomes structurally organize centromeric DNA to promote KT formation. In humans, CenH3 associates with centromeric ␣ satellite repeats (5), resulting in megabase expanses of centromeric nucleosomes. These centromeric nucleosomes drive the assembly of the KT structure that interacts with multiple microtubules. However, the number of CenH3 nucleosomes far exceeds the number of microtubules associated with a CEN, making the minimal number and arrangement of CenH3 nucleosomes necessary to assemble a single functional KT unclear. In flies and humans, blocks of CenH3 nucleosomes are interspersed with blocks of H3 nucleosomes (6), suggesting that higher order folding of the centromeric

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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

Furuyama

Biggins

2007

Proc. Natl. Acad. Sci. U.S.A.

240

216

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“…Based on a variety of experiments involving bulk chromatin, it has been long believed that in S phase, nucleosomes deposited on newly synthesized DNA are generated from newly synthesized histones and do not involve histone subunits from preexisting nucleosomes (2,(4)(5)(6)(7)(8). A recent paper focusing on the histone variant H3.1, which is deposited specifically during DNA replication, revealed that newly synthesized H3.1 did not form mixed tetramers with preexisting H3 molecules, confirming that nucleosomes are conservatively inherited during DNA replication (13).…”

Section: Discussionmentioning

confidence: 99%

“…In the semiconservative model, the resulting tetramers would bear a mixture of old and new histones, allowing transmission of epigenetic information within the basic nucleosome unit. Though mechanistically attractive, the mixed tetramer model received little support from a variety of studies, which failed to detect old and new H3-H4 dimers within the same nucleosome (2,(4)(5)(6)(7)(8). A notable exception was an analysis of active chromatin from chicken cells suggesting substantial levels of mixed tetramers (9).…”

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confidence: 99%

Splitting of H3–H4 tetramers at transcriptionally active genes undergoing dynamic histone exchange

Katan-Khaykovich

Struhl

2011

Proc. Natl. Acad. Sci. U.S.A.

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Nucleosome deposition occurs on newly synthesized DNA during DNA replication and on transcriptionally active genes via nucleosome-remodeling complexes recruited by activator proteins and elongating RNA polymerase II. It has been long believed that histone deposition involves stable H3-H4 tetramers, such that newly deposited nucleosomes do not contain H3 and H4 molecules with their associated histone modifications from preexisting nucleosomes. However, biochemical analyses and recent experiments in mammalian cells have raised the idea that preexisting H3-H4 tetramers might split into dimers, resulting in mixed nucleosomes composed of "old" and "new" histones. It is unknown to what extent different genomic loci might utilize such a mechanism and under which circumstances. Here, we address whether tetramer splitting occurs in a locus-specific manner by using sequential chromatin immunoprecipitation of mononucleosomes from yeast cells containing two differentially tagged versions of H3 that are expressed "old" and "new" histones. At many genomic loci, we observe little or no nucleosomal cooccupancy of old and new H3, indicating that tetramer splitting is generally infrequent. However, cooccupancy is detected at highly active genes, which have a high rate of histone exchange. Thus, DNA replication largely results in nucleosomes bearing exclusively old or new H3-H4, thereby precluding the acquisition of new histone modifications based on preexisting modifications within the same nucleosome. In contrast, tetramer splitting, dimer exchange, and nucleosomes with mixed H3-H4 tetramers occur at highly active genes, presumably linked to rapid histone exchange associated with robust transcription.T he packaging of eukaryotic DNA into chromatin influences many DNA-associated processes, including transcriptional regulation. Within the chromatin fiber, each basic nucleosome unit bears important chemical and structural information. The mechanisms by which nucleosomes are assembled on DNA during replication, transcription, DNA repair, etc., can thus impact not only the integrity of chromatin structure but also patterns of gene expression and epigenetic inheritance. The H3-H4 tetramer core of each nucleosome is the more stable component and contains most of the relatively persistent and functionally important histone methylation marks. Much attention has therefore been given to the questions of how the H3-H4 tetramers are formed and maintained on chromatin.Early studies attempted to distinguish between a conservative assembly model, by which old and new histones form separate tetramers on replicating DNA, and a semiconservative assembly mechanism, by which existing tetramers are split into H3-H4 dimers, followed by association of new H3-H4 dimers to complete each nucleosome core (1-3). In the semiconservative model, the resulting tetramers would bear a mixture of old and new histones, allowing transmission of epigenetic information within the basic nucleosome unit. Though mechanistically attractive, the mixed tetramer model receiv...

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“…Sedimentation studies with heavy isotope-labeled histones indicated that histone octamers segregate in a conserved manner [19]. These findings led to the nucleosome conservative segregation model.…”

Section: Introductionmentioning

confidence: 96%

Epigenetic inheritance: Uncontested?

Reinberg

2011

Cell Res

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"Epigenetics" is currently defined as "the inheritance of variation (-genetics) above and beyond (epi-) changes in the DNA sequence". Despite the fact that histones are believed to carry important epigenetic information, little is known about the molecular mechanisms of the inheritance of histone-based epigenetic information, including histone modifications and histone variants. Here we review recent progress and discuss potential models for the mitotic inheritance of histone modifications-based epigenetic information.

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Conservative assembly and segregation of nucleosomal histories

Cited by 168 publications

References 21 publications

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

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

Splitting of H3–H4 tetramers at transcriptionally active genes undergoing dynamic histone exchange

Epigenetic inheritance: Uncontested?

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