Single residues in the histone core domain guide transcription
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ABSTRACT:
PROVIDER: PRJNA1174139 | ENA |
REPOSITORIES: ENA
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Project description:Single residues in the histone core domain guide transcription elongation
| PRJNA1177433 | ENA
Project description:The nucleosome is thought to suppress transcription in eukaryotes by acting as a structural barrier. However, once begun, transcription can readily proceed in the presence of nucleosomes, suggesting this model is insufficient. Here, we establish that the ultra-conserved core domain of the ancestral histone H2A.Z informs transcription elongation via direct interaction of its loop 2 region with the transcription elongation factor Spt6. Interrogating H2A.Z sequences representing more than a billion years of eukaryotic evolution in a single synthetic host, we show that Spt6 can distinguish even single-residue substitutions within their loop 2, controlling RNAPII processivity. Our results place the histone core domain at the origin of eukaryotic gene expression, establishing it as a powerful force shaping transcription.
2025-06-30 | GSE279717 | GEO
Project description:Transcription activity is tightly correlated with a stereotypical suite of chromatin features and modifications, but how/if these are interpreted by transcriptional machinery remains poorly understood. The presence of the histone variants such as H2A.Z is one such feature, known to change the biophysical properties of chromatin. Here we couple phylogenetic analysis to synthetic biology to establish that H2A.Z tunes RNA polymerase II elongation activity through a direct interaction with the transcription machinery. We show that evolution-derived sequence variation in only seven residues located in the short unstructured loop 2 (L2) region of H2A.Z affects RNA polymerase II elongation rates through physical interaction with transcription elongation factor Spt6. Our results establish a direct physical and functional link between transcription and its chromatinized template. Moreover, we proposed that species-specific variations in H2A.Z L2 change the ground state level of transcription and could be exploited for the creation of emergent properties of chromatin.
2025-06-30 | GSE280242 | 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: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
Project description:Histones are among the most conserved proteins known, but organismal differences do exist. In this study we examined the contribution that divergent amino acids within histone H3 make to cell growth and chromatin structure in S. cerevisiae. We show that, while amino acids that define histone H3.3 are dispensable for yeast growth, substitution of residues within the histone H3 alpha 3 helix with the human counterparts results in a severe growth defect. Mutations within this domain also result in altered nucleosome positioning, both in vivo and in vitro, which is accompanied by increased preference for nucleosome favoring sequences. These results suggest that divergent amino acids within the histone H3 alpha 3 helix play organismal roles in defining chromatin structure. Mnase-seq for two replicates each of wildtype and H3 c-terminal mutants.
2015-11-10 | E-GEOD-73425 | biostudies-arrayexpress
Project description:We report the acetylation of lysine residues in the globular domain of H3 (H3K64ac and H3K122ac) marks active gene promoters and also a subset of active enhancers in mouse embryonic stem cells (mESCs), human erythroleukemic cell line (K562). Moreover, we find a novel class of active functional enhancers in ESCs that are marked by H3K122ac but which lack H3K27ac. This work suggests that a more complex analysis of histone acetylation is required to identify enhancers than was previously considered. Examination of histone modifications in mouse ESCs (2 biological replicates) and K562 cells
2016-03-12 | E-GEOD-66023 | biostudies-arrayexpress
Project description:Nucleosome assembly in vivo requires assembly factors, such as histone chaperones, to bind to histones and mediate their deposition onto DNA. In yeast, the essential histone chaperone FACT (FAcilitates Chromatin Transcription) functions in nucleosome assembly and H2A-H2B deposition during transcription elongation and DNA replication. Recent studies have identified candidate histone residues that mediate FACT binding to histones, but it is not known which histone residues are important for FACT to deposit histones onto DNA during nucleosome assembly. In this study, we report that the histone H2B repression (HBR) domain within the H2B N-terminal tail is important for histone deposition by FACT. Deletion of the HBR domain causes significant defects in histone occupancy in the yeast genome, particularly at HBR-repressed genes, and a pronounced increase in H2A-H2B dimers that remain bound to FACT in vivo. Moreover, the HBR domain is required for purified FACT to efficiently assemble recombinant nucleosomes in vitro. We propose that the interaction between the highly basic HBR domain and DNA plays an important role in stabilizing the nascent nucleosome during the process of histone H2A-H2B deposition by FACT. 6 samples, 2 inputs and 4 ChIP samples for histone H2B (2 for wild-type and 2 for an H2B â30-37 mutant)
2016-08-10 | E-GEOD-80831 | biostudies-arrayexpress
Project description:Histones are among the most conserved proteins known, but organismal differences do exist. In this study we examined the contribution that divergent amino acids within histone H3 make to cell growth and chromatin structure in S. cerevisiae. We show that, while amino acids that define histone H3.3 are dispensable for yeast growth, substitution of residues within the histone H3 alpha 3 helix with the human counterparts results in a severe growth defect. Mutations within this domain also result in altered nucleosome positioning, both in vivo and in vitro, which is accompanied by increased preference for nucleosome favoring sequences. These results suggest that divergent amino acids within the histone H3 alpha 3 helix play organismal roles in defining chromatin structure.
2015-11-10 | GSE73425 | GEO
Project description:Nucleosome assembly in vivo requires assembly factors, such as histone chaperones, to bind to histones and mediate their deposition onto DNA. In yeast, the essential histone chaperone FACT (FAcilitates Chromatin Transcription) functions in nucleosome assembly and H2A-H2B deposition during transcription elongation and DNA replication. Recent studies have identified candidate histone residues that mediate FACT binding to histones, but it is not known which histone residues are important for FACT to deposit histones onto DNA during nucleosome assembly. In this study, we report that the histone H2B repression (HBR) domain within the H2B N-terminal tail is important for histone deposition by FACT. Deletion of the HBR domain causes significant defects in histone occupancy in the yeast genome, particularly at HBR-repressed genes, and a pronounced increase in H2A-H2B dimers that remain bound to FACT in vivo. Moreover, the HBR domain is required for purified FACT to efficiently assemble recombinant nucleosomes in vitro. We propose that the interaction between the highly basic HBR domain and DNA plays an important role in stabilizing the nascent nucleosome during the process of histone H2A-H2B deposition by FACT.
2016-08-10 | GSE80831 | GEO