Similar Datasets
Project description:Gene network transitions in embryos and other fate-changing contexts involve combinations of transcription factors. A subset of fate-changing transcription factors act as pioneers; they scan and target nucleosomal DNA and initiate cooperative events that can open the local chromatin. However, a gap has remained in understanding how molecular interactions with the nucleosome contribute to the chromatin-opening phenomenon. Here we identified a short α-helical region, conserved among FOXA pioneer factors, that interacts with core histones and contributes to chromatin opening in vitro. The same domain is involved in chromatin opening in early mouse embryos for normal development. Thus, local opening of chromatin by interactions between pioneer factors and core histones promotes genetic programming.
| S-EPMC7901023 | biostudies-literature
Project description:Gene network transitions in embryos and fate-changing contexts involve combinations of transcription factors. A subset of fate-changing transcription factors act as pioneers; they scan and target nucleosomal DNA and initiate cooperative events that can open the local chromatin. But a gap has remained in understanding how molecular interactions with the nucleosome, beyond interactions with the DNA helix, contribute to the chromatin opening phenomenon. Here we identified a short alpha-helical region, conserved among FoxA pioneer factors and separated from the DNA binding domain, that interacts with core histones and is necessary for chromatin opening in vitro. The same domain is necessary for chromatin opening in early mouse embryos and for normal embryonic development and viability. Thus, local opening of chromatin by interactions between pioneer factors and core histones is crucial for genetic programming.
2020-01-22 | GSE134464 | GEO
Project description:Gene network transitions in embryos and fate-changing contexts involve combinations of transcription factors. A subset of fate-changing transcription factors act as pioneers; they scan and target nucleosomal DNA and initiate cooperative events that can open the local chromatin. But a gap has remained in understanding how molecular interactions with the nucleosome, beyond interactions with the DNA helix, contribute to the chromatin opening phenomenon. Here we identified a short alpha-helical region, conserved among FoxA pioneer factors and separated from the DNA binding domain, that interacts with core histones and is necessary for chromatin opening in vitro. The same domain is necessary for chromatin opening in early mouse embryos and for normal embryonic development and viability. Thus, local opening of chromatin by interactions between pioneer factors and core histones is crucial for genetic programming.
2020-01-22 | GSE134463 | GEO
Project description:Gene Network Transitions in Embryos Depend Upon Interactions between a Pioneer Transcription Factor and Core Histones
| PRJNA555189 | ENA
Project description:Gene Network Transitions in Embryos Depend Upon Interactions between a Pioneer Transcription Factor and Core Histones [ATAC-Seq]
| PRJNA555197 | ENA
Project description:Gene Network Transitions in Embryos Depend Upon Interactions between a Pioneer Transcription Factor and Core Histones [RNA-Seq]
| PRJNA555196 | ENA
Project description:Cells in renewing tissues exhibit dramatic transcriptional changes as they differentiate. The contribution of chromatin looping to tissue renewal is incompletely understood. Enhancer-promoter interactions could be relatively stable as cells transition from progenitor to differentiated states; alternatively, chromatin looping could be as dynamic as the gene expression from their loci. The intestinal epithelium is the most rapidly renewing mammalian tissue. Proliferative cells in crypts of Lieberkühn sustain a stream of differentiated cells that are continually shed into the lumen. We apply chromosome conformation capture combined with chromatin immunoprecipitation (HiChIP) and sequencing to measure enhancer-promoter interactions in progenitor and differentiated cells of the intestinal epithelium. Despite dynamic gene regulation across the differentiation axis, we find that enhancer-promoter interactions are relatively stable. Functionally, we find HNF4 transcription factors are required for chromatin looping at target genes. Depletion of HNF4 disrupts local chromatin looping, histone modifications, and target gene expression. This study provides insights into transcriptional regulatory mechanisms governing homeostasis in renewing tissues.
| S-EPMC7899294 | biostudies-literature
Project description:Pob3p is an essential component of the S. cerevisiae FACT complex (yFACT). Several lines of evidence indicate that the yFACT complex plays an important role in chromatin assembly including the observation that the pob3 Q308K allele is synthetically lethal with an allele of histone H4 that prevents the diacetylation of newly synthesized molecules. We have analyzed the genetic interactions between the Q308K allele of POB3 and mutations in all of the sites of acetylation that have been identified on newly synthesized histones. Genetic interactions were observed between POB3 and sites of acetylation on the NH(2)-terminal tails of H3 and H4. For histone H3, lysine residues 14 and 23 were particularly important when POB3 activity is compromised. Surprisingly, synthetic defects observed when the pob3 Q308K allele was combined with mutations of H4 lysines 5 and 12, were not phenocopied by deletion of HAT1, which encodes the enzyme that is thought to generate this pattern of acetylation on H4. Genetic interactions were also observed between POB3 and sites of acetylation found in the core domain of newly synthesized histones H3 and H4. These include synthetic lethality with an allele of H4 lysine 91 that mimics constitutive acetylation. While the mutations that alter H4 lysines 5, 12 and 91 do not affect binding to Pob3p, mutation of histone H3 lysine 56 decreases the association of histones with Pob3p. These results support the model that the yFACT complex plays a central role in chromatin assembly pathways regulated by acetylation of newly synthesized histones.
| S-EPMC3142300 | biostudies-literature
Project description:There are some functional compatibilities between upstream and core promoter sequences for transcriptional activation in yeast, Drosophila and mammalian cells. Here we examined whether similar compatibilities exist in sea urchin embryos, and if so, whether they are dynamically regulated during early development. Two reporter plasmids, each containing a test promoter conjugated to either CFP or YFP, were concurrently introduced into embryos, and their expression patterns were studied by fluorescence microscopy. The upstream sequence of the Hemicentrotus pulcherrimus (Hp) OtxE promoter drives the expression of its own core promoter and that of Strongylocentrotus purpuratus (Sp) Spec2a in different embryonic regions, especially at the late gastrula stage. Interestingly, when the four putative transcription factor binding sites of this upstream sequence were individually mutated, the resulting sequences directed different spatiotemporal expression from the same set of two core promoters, indicating that combinations of upstream factors may determine core promoter usage in sea urchin embryos. In addition, the insertion or deletion of consensus or nonconsensus TATA sequences changed the expression profile significantly, irrespective of whether the upstream sequence was intact or mutated. Thus, the TATA sequence may serve as a primary determinant for core promoter selection in these cells.
| S-EPMC1950538 | biostudies-literature
Project description:Mutations conferring resistance to one antibiotic can increase (cross-resistance) or decrease (collateral sensitivity) resistance to others. Antibiotic combinations displaying collateral sensitivity could be used in treatments that slow resistance evolution. However, lab-to-clinic translation requires understanding whether collateral effects are robust across different environmental conditions. Here, we isolated and characterized resistant mutants of Escherichia coli using five antibiotics, before measuring collateral effects on resistance to other paired antibiotics. During both isolation and phenotyping, we varied conditions in ways relevant in nature (pH, temperature, and bile). This revealed that local abiotic conditions modified expression of resistance against both the antibiotic used during isolation and other antibiotics. Consequently, local conditions influenced collateral sensitivity in two ways: by favoring different sets of mutants (with different collateral sensitivities) and by modifying expression of collateral effects for individual mutants. These results place collateral sensitivity in the context of environmental variation, with important implications for translation to real-world applications. IMPORTANCE When bacteria become resistant to an antibiotic, the genetic changes involved sometimes increase (cross-resistance) or decrease (collateral sensitivity) their resistance to other antibiotics. Antibiotic combinations showing repeatable collateral sensitivity could be used in treatment to slow resistance evolution. However, collateral sensitivity interactions may depend on the local environmental conditions that bacteria experience, potentially reducing repeatability and clinical application. Here, we show that variation in local conditions (pH, temperature, and bile salts) can influence collateral sensitivity in two ways: by favoring different sets of mutants during bacterial resistance evolution (with different collateral sensitivities to other antibiotics) and by modifying expression of collateral effects for individual mutants. This suggests that translation from the lab to the clinic of new approaches exploiting collateral sensitivity will be influenced by local abiotic conditions.
| S-EPMC8631318 | biostudies-literature