Similar Datasets
Project description:We have performed a comprehensive analysis of the involvement of histone H3 and H4 residues in the regulation of chronological lifespan in yeast. Residues where substitution resulted in the most pronounced lifespan extension are all on the exposed face of the nucleosome, with the exception of H3E50, which is present on the lateral surface, between two DNA gyres. Other residues that had a more modest effect on lifespan extension were concentrated at the extremities of the H3-H4 dimer, suggesting a role in stabilizing the dimer in its nucleosome frame. Residues implicated in a reduced lifespan were buried in the histone handshake motif, suggesting that these mutations destabilize the octamer structure. All residues exposed on the disk and that caused lifespan extension are known to interact with Sir3. We find that substitution of H4K16 and H4H18 cause Sir3 to redistribute from telomeres and silent mating loci to secondary positions, often enriched for Rap1 or Abf1 binding sites, whereas H3E50 does not. The redistributed Sir3 cause transcriptional repression at most of the new loci, including of genes where null mutants were previously shown to extend chronological lifespan. The transcriptomic profiles of H4K16 and H4H18 mutant strains are very similar, and compatible with a DNA replication stress response. This is distinct from the transcriptomic profile of H3E50, which matches strong induction of oxidative phosphorylation. We propose that different clusters of H3 and H4 residues are involved in either binding to non-histone proteins, or in destabilizing the association of the nucleosome DNA, or disrupting binding of a H3-H4 dimer in the nucleosome, or disturbing the structural stability of the octamer, each category impacting on chronological lifespan through a different path.
2019-11-09 | GSE140160 | GEO
Project description:We have performed a comprehensive analysis of the involvement of histone H3 and H4 residues in the regulation of chronological lifespan in yeast. Residues where substitution resulted in the most pronounced lifespan extension are all on the exposed face of the nucleosome, with the exception of H3E50, which is present on the lateral surface, between two DNA gyres. Other residues that had a more modest effect on lifespan extension were concentrated at the extremities of the H3-H4 dimer, suggesting a role in stabilizing the dimer in its nucleosome frame. Residues implicated in a reduced lifespan were buried in the histone handshake motif, suggesting that these mutations destabilize the octamer structure. All residues exposed on the disk and that caused lifespan extension are known to interact with Sir3. We find that substitution of H4K16 and H4H18 cause Sir3 to redistribute from telomeres and silent mating loci to secondary positions, often enriched for Rap1 or Abf1 binding sites, whereas H3E50 does not. The redistributed Sir3 cause transcriptional repression at most of the new loci, including of genes where null mutants were previously shown to extend chronological lifespan. The transcriptomic profiles of H4K16 and H4H18 mutant strains are very similar, and compatible with a DNA replication stress response. This is distinct from the transcriptomic profile of H3E50, which matches strong induction of oxidative phosphorylation. We propose that different clusters of H3 and H4 residues are involved in either binding to non-histone proteins, or in destabilizing the association of the nucleosome DNA, or disrupting binding of a H3-H4 dimer in the nucleosome, or disturbing the structural stability of the octamer, each category impacting on chronological lifespan through a different path.
2019-12-03 | GSE141306 | GEO
Project description:We have performed a comprehensive analysis of the involvement of histone H3 and H4 residues in the regulation of chronological lifespan in yeast. Residues where substitution resulted in the most pronounced lifespan extension are all on the exposed face of the nucleosome, with the exception of H3E50, which is present on the lateral surface, between two DNA gyres. Other residues that had a more modest effect on lifespan extension were concentrated at the extremities of the H3-H4 dimer, suggesting a role in stabilizing the dimer in its nucleosome frame. Residues implicated in a reduced lifespan were buried in the histone handshake motif, suggesting that these mutations destabilize the octamer structure. All residues exposed on the disk and that caused lifespan extension are known to interact with Sir3. We find that substitution of H4K16 and H4H18 cause Sir3 to redistribute from telomeres and silent mating loci to secondary positions, often enriched for Rap1 or Abf1 binding sites, whereas H3E50 does not. The redistributed Sir3 cause transcriptional repression at most of the new loci, including of genes where null mutants were previously shown to extend chronological lifespan. The transcriptomic profiles of H4K16 and H4H18 mutant strains are very similar, and compatible with a DNA replication stress response. This is distinct from the transcriptomic profile of H3E50, which matches strong induction of oxidative phosphorylation. We propose that different clusters of H3 and H4 residues are involved in either binding to non-histone proteins, or in destabilizing the association of the nucleosome DNA, or disrupting binding of a H3-H4 dimer in the nucleosome, or disturbing the structural stability of the octamer, each category impacting on chronological lifespan through a different path.
2019-12-13 | GSE141973 | GEO
Project description:We have performed a comprehensive analysis of the involvement of histone H3 and H4 residues in the regulation of chronological lifespan in yeast. Residues where substitution resulted in the most pronounced lifespan extension are all on the exposed face of the nucleosome, with the exception of H3E50, which is present on the lateral surface, between two DNA gyres. Other residues that had a more modest effect on lifespan extension were concentrated at the extremities of the H3-H4 dimer, suggesting a role in stabilizing the dimer in its nucleosome frame. Residues implicated in a reduced lifespan were buried in the histone handshake motif, suggesting that these mutations destabilize the octamer structure. All residues exposed on the disk and that caused lifespan extension are known to interact with Sir3. We find that substitution of H4K16 and H4H18 cause Sir3 to redistribute from telomeres and silent mating loci to secondary positions, often enriched for Rap1 or Abf1 binding sites, whereas H3E50 does not. The redistributed Sir3 cause transcriptional repression at most of the new loci, including of genes where null mutants were previously shown to extend chronological lifespan. The transcriptomic profiles of H4K16 and H4H18 mutant strains are very similar, and compatible with a DNA replication stress response. This is distinct from the transcriptomic profile of H3E50, which matches strong induction of oxidative phosphorylation. We propose that different clusters of H3 and H4 residues are involved in either binding to non-histone proteins, or in destabilizing the association of the nucleosome DNA, or disrupting binding of a H3-H4 dimer in the nucleosome, or disturbing the structural stability of the octamer, each category impacting on chronological lifespan through a different path.
2019-12-03 | GSE141317 | GEO
Project description:Structural clusters of histone H3 and H4 residues regulate chronological lifespan in Saccharomyces cerevisiae
| PRJNA595481 | ENA
Project description:Structural clusters of histone H3 and H4 residues regulate chronological lifespan in Saccharomyces cerevisiae [Other]
| PRJNA588445 | ENA
Project description:Structural clusters of histone H3 and H4 residues regulate chronological lifespan in Saccharomyces cerevisiae [ChIP-seq]
| PRJNA593029 | ENA
Project description:Structural clusters of histone H3 and H4 residues regulate chronological lifespan in Saccharomyces cerevisiae [RNA-seq]
| PRJNA595485 | ENA
Project description:Structural clusters of histone H3 and H4 residues regulate chronological lifespan in Saccharomyces cerevisiae [Sir3 ChIP-seq]
| PRJNA593048 | ENA
Project description:The biological significance of recently described modifiable residues in the globular core of the bovine nucleosome remains elusive. We have mapped these modification sites onto the Saccharomyces cerevisiae histones and used a genetic approach to probe their potential roles both in heterochromatic regions of the genome and in the DNA repair response. By mutating these residues to mimic their modified and unmodified states, we have generated a total of 39 alleles affecting 14 residues in histones H3 and H4. Remarkably, despite the apparent evolutionary pressure to conserve these near-invariant histone amino acid sequences, the vast majority of mutant alleles are viable. However, a subset of these variant proteins elicit an effect on transcriptional silencing both at the ribosomal DNA locus and at telomeres, suggesting that posttranslational modification(s) at these sites regulates formation and/or maintenance of heterochromatin. Furthermore, we provide direct mass spectrometry evidence for the existence of histone H3 K56 acetylation in yeast. We also show that substitutions at histone H4 K91, K59, S47, and R92 and histone H3 K56 and K115 lead to hypersensitivity to DNA-damaging agents, linking the significance of the chemical identity of these modifiable residues to DNA metabolism. Finally, we allude to the possible molecular mechanisms underlying the effects of these modifications.
| S-EPMC1280264 | biostudies-literature