Normal stoichiometry of histone dimer sets is necessary for high fidelity of mitotic chromosome transmission

Meeks-Wagner, Douglas; Hartwell, Leland H.

doi:10.1016/0092-8674(86)90483-6

Cited by 315 publications

(231 citation statements)

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“…Many in vivo studies have been performed on the new nature of core histones-in addition to the vital role in chromatin organization mentioned above, especially in yeasts (Hereford et al 1982;Meeks-Wagner & Hartwell 1986;Norris & Osley 1987;Osley & Lycan 1987;Clark-Adams et al 1988;Norris et al 1988;Grunstein 1990;Carr et al 1994;Hirschhorn et al 1995)because gene replacement experiments on them can be carried out easily. Moreover, it has been reported that in Saccharomyces cerevisiae, the deletion of H4 N-terminal residues 4-23 or mutagenesis of the acetylatable lysines in this region decreases the activation of the GAL1 promoter, while the deletion of N-terminal residues 4-15 of H3 or the mutagenesis of the acetylatable lysines causes a hyperactivation of GAL1 (Fisher-Adams & Grunstein 1995).…”

Section: Introductionmentioning

confidence: 99%

A single copy of linker H1 genes is enough for proliferation of the DT40 chicken B cell line, and linker H1 variants participate in regulation of gene expression

Yasuda

Nakayama

1997

Genes to Cells

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Background: There is general agreement that large numbers of histone H1 are necessary for maintenance of the higher order structure of chromatin in higher eukaryotes. The chicken H1 gene family comprises six members per haploid genome, the total copy number being 12, and they encode six H1 variants which are considerably different from each other in amino acid sequence. We recently established that in two chicken DT40 mutants (1/ 2D110kb and D57kb), which lack, respectively, one allele of the gene cluster of 110 kb carrying six H1 genes, plus 33 core histone genes, and two copies each of four of the six H1 genes included in an Ϸ 57 kb segment of the cluster, expression of the remaining H1 genes is increased, resulting in constant steady-state levels of total H1 mRNAs. These results gave rise to the simple questions of how many H1 genes and how many H1 variants, at minimum, are necessary for the viability of DT40 cells.

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Section: Introductionmentioning

confidence: 99%

A single copy of linker H1 genes is enough for proliferation of the DT40 chicken B cell line, and linker H1 variants participate in regulation of gene expression

Yasuda

Nakayama

1997

Genes to Cells

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“…The last work (19) also suggested how the cell may regulate the formation of nucleosomes. Chromosome loss was increased only when H2A and H2B were jointly overexpressed and not when either protein was overexpressed individually.…”

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confidence: 99%

“…Second, H2B may be required for mitosis, since a strain bearing a conditionally expressed HTB2 gene arrests late in the cell cycle when the synthesis of H2B is turned off (6). Finally, the maintenance of normal H2A-H2B dimer stoichiometry is a prerequisite for proper chromosome segregation, since overexpression of the genes for H2A and H2B decreases the fidelity of mitotic chromosome transmission (19).…”

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confidence: 99%

The two gene pairs encoding H2A and H2B play different roles in the Saccharomyces cerevisiae life cycle.

Norris¹,

Osley²

1987

Mol. Cell. Biol.

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We have isolated Saccharomyces cerevisiae mutants bearing deletions of one or the other of the two divergently transcribed gene pairs encoding H2A and H2B. The deletions produced diverse effects on the yeast life cycle. Deletion of TRT1, one of the H2A-H2B gene pair sets, affected mitotic growth, sporulation, spore germination, the heat shock response, and exit from the stationary phase; deletion of TRT2, the other H2A-H2B gene pair set, had negligible effects on these same processes. Using a genetic complementation assay, we found that the differential effects of the deletions could be attributed to two features of the gene sets: first, the expression of the TRTI gene pair, but not the TRT2 gene pair, could compensate for the absence of its partner; second, the protein subtypes encoded by the two gene pairs appear to have different functions in the heat shock response.Most DNA in eucaryotic chromosomes is associated with four core histones in a structure known as the nucleosome (18). It has long been assumed, but until recently never directly demonstrated, that nucteosomes are essential for chromosomes to function properly. The discovery that Saccharomyces cerevisiae contains only two genes for each core histone has made it possible to assess the in vivo function of nucleosomes by genetic analysis (10). Three points have emerged from such studies. First, H2A and H2B are essential proteins in yeast, since strains bearing frameshift mutations in both copies of the genes encoding H2A (HTAI and HTA2) or the genes encoding H2B (HTBI and HTB2) are inviable (5,15,25). Second, H2B may be required for mitosis, since a strain bearing a conditionally expressed HTB2 gene arrests late in the cell cycle when the synthesis of H2B is turned off (6). Finally, the maintenance of normal H2A-H2B dimer stoichiometry is a prerequisite for proper chromosome segregation, since overexpression of the genes for H2A and H2B decreases the fidelity of mitotic chromosome transmission (19).The last work (19) also suggested how the cell may regulate the formation of nucleosomes. Chromosome loss was increased only when H2A and H2B were jointly overexpressed and not when either protein was overexpressed individually. This result implies that the H2A-H2B dimer, and not H2A or H2B alone, regulates nucleosome formation in vivo. A regulatory role for the H2A-H2B dimer may also be reflected in the genomic arrangement of the HTA and HTB genes in yeast. These genes are located in two divergently transcribed TRT loci (TRTJ and TRT2), each of which contains one HTA gene and one HTB gene (Fig. 1A and B) (10). We have shown that the HTA and HTB genes at each locus are expressed at the same time during the cell cycle and that the genes at TRT1 are regulated by the same promoter elements (9,11,21). This observation, coupled with the apparent regulatory role of the H2A-H2B dimer, suggests that it may be more accurate to consider the TRT loci rather than the individual HTA and HTB genes as the regulatory units for H2A and H2B production. * Corresponding author...

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“…Dysregulation of histone expression has been linked with increased mitotic chromosome loss and DNA damage sensitivity, resulting in genomic instability (22,23), depending on the types or contexts of the histones (22). In this study, we noted that enforced expression of H2A or H2AX did not profoundly affect any cell function, although a slight delay of cell proliferation was observed (Fig.…”

Section: Discussionmentioning

confidence: 49%

Mammal-specific H2A Variant, H2ABbd, Is Involved in Apoptotic Induction via Activation of NF-κB Signaling Pathway

Goshima

Shimada

Sharif

et al. 2014

Journal of Biological Chemistry

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Background:H2ABbd is an H2A variant possessing a highly divergent structure. However, the in vivo function of H2ABbd is not understood. Results: Expression of H2ABbd caused DNA damage, induced apoptotis, and finally led to cell death. Conclusion: H2ABbd caused apoptosis in caspase 3-and NF-B-dependent manners. Significance: This work describes a novel role for human H2ABbd in gene regulation and cell death.

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Normal stoichiometry of histone dimer sets is necessary for high fidelity of mitotic chromosome transmission

Cited by 315 publications

References 35 publications

A single copy of linker H1 genes is enough for proliferation of the DT40 chicken B cell line, and linker H1 variants participate in regulation of gene expression

A single copy of linker H1 genes is enough for proliferation of the DT40 chicken B cell line, and linker H1 variants participate in regulation of gene expression

The two gene pairs encoding H2A and H2B play different roles in the Saccharomyces cerevisiae life cycle.

Mammal-specific H2A Variant, H2ABbd, Is Involved in Apoptotic Induction via Activation of NF-κB Signaling Pathway

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