Structural mapping of regulatory function of histone H3 and H4 residues
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PROVIDER: PRJNA140247 | ENA |
REPOSITORIES: ENA
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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:Nucleosome structure directly influences gene transcription. However, the function of each histone residue remains largely unknown. Here we profiled gene expression changes upon the mutation of individual residues of histone H3 and H4. Histone residues grouped by expression change similarity displayed overall structural relevance. This regulatory functional map of the core histones led to novel findings. First, the residues specific to each histone family tend to be more influential than those commonly found among different histones. Second, unlike histone acetylations, H3K4 trimethylation does not appear to be prerequisite for gene activation. Third, H3Q5 has been newly identified for its putative interactions with many chromatin regulators for transcription control. Lastly, the nucleosome lateral surface seems to play a key role through interactions with the surrounding DNA. Remarkably, we discovered a novel role for H3K56 in chromatin dynamics. The deletion of this residue, but not the alteration of acetylation states, caused a genome-wide decrease in nucleosome mobility and stabilized nucleosome positioning near transcription start and end sites. Occupying the DNA entry/exit site, H3K56 is thought to modulate nucleosome sliding along DNA. Taken together, genomics approaches such as microarray and deep sequencing prove valuable for mapping the function of histone residues. Microarray analysis was performed for 123 histone mutants and four wild-types as two reaplications of H3 and H4 of Saccharomyces ceravisiae.
2012-12-05 | E-GEOD-29059 | biostudies-arrayexpress
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:Nucleosome structure directly influences gene transcription. However, the function of each histone residue remains largely unknown. Here we profiled gene expression changes upon the mutation of individual residues of histone H3 and H4. Histone residues grouped by expression change similarity displayed overall structural relevance. This regulatory functional map of the core histones led to novel findings. First, the residues specific to each histone family tend to be more influential than those commonly found among different histones. Second, unlike histone acetylations, H3K4 trimethylation does not appear to be prerequisite for gene activation. Third, H3Q5 has been newly identified for its putative interactions with many chromatin regulators for transcription control. Lastly, the nucleosome lateral surface seems to play a key role through interactions with the surrounding DNA. Remarkably, we discovered a novel role for H3K56 in chromatin dynamics. The deletion of this residue, but not the alteration of acetylation states, caused a genome-wide decrease in nucleosome mobility and stabilized nucleosome positioning near transcription start and end sites. Occupying the DNA entry/exit site, H3K56 is thought to modulate nucleosome sliding along DNA. Taken together, genomics approaches such as microarray and deep sequencing prove valuable for mapping the function of histone residues. SUBMITTER_CITATION: Global Mapping of the Regulatory Interactions of Histone Residues, Epigenomics Keystone Symposium, January 21th (2012).
2012-12-05 | GSE29059 | GEO