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Project description:BackgroundDuring eye lens development the embryonic vasculature regresses leaving the lens without a direct oxygen source. Both embryonically and throughout adult life, the lens contains a decreasing oxygen gradient from the surface to the core that parallels the natural differentiation of immature surface epithelial cells into mature core transparent fiber cells. These properties of the lens suggest a potential role for hypoxia and the master regulator of the hypoxic response, hypoxia-inducible transcription factor 1 (HIF1), in the regulation of genes required for lens fiber cell differentiation, structure and transparency. Here, we employed a multiomics approach combining CUT&RUN, RNA-seq and ATACseq analysis to establish the genomic complement of lens HIF1α binding sites, genes activated or repressed by HIF1α and the chromatin states of HIF1α-regulated genes.ResultsCUT&RUN analysis revealed 8375 HIF1α-DNA binding complexes in the chick lens genome. One thousand one hundred ninety HIF1α-DNA binding complexes were significantly clustered within chromatin accessible regions (χ2 test p < 1 × 10- 55) identified by ATACseq. Formation of the identified HIF1α-DNA complexes paralleled the activation or repression of 526 genes, 116 of which contained HIF1α binding sites within 10kB of the transcription start sites. Some of the identified HIF1α genes have previously established lens functions while others have novel functions never before examined in the lens. GO and pathway analysis of these genes implicate HIF1α in the control of a wide-variety of cellular pathways potentially critical for lens fiber cell formation, structure and function including glycolysis, cell cycle regulation, chromatin remodeling, Notch and Wnt signaling, differentiation, development, and transparency.ConclusionsThese data establish the first functional map of genomic HIF1α-DNA complexes in the eye lens. They identify HIF1α as an important regulator of a wide-variety of genes previously shown to be critical for lens formation and function and they reveal a requirement for HIF1α in the regulation of a wide-variety of genes not yet examined for lens function. They support a requirement for HIF1α in lens fiber cell formation, structure and function and they provide a basis for understanding the potential roles and requirements for HIF1α in the development, structure and function of more complex tissues.
| S-EPMC8254356 | biostudies-literature
Project description:Background: During eye lens development the fetal vasculature regresses leaving the lens without a direct oxygen source. Both embryonically and throughout adult life, the lens contains a decreasing oxygen gradient from the surface to the core that parallels the natural differentiation of immature surface epithelial cells into mature core transparent fiber cells. These properties of the lens suggest a potential role for hypoxia in the regulation of genes required for mature lens structure and function. Since HIF1α is a master regulator of the hypoxic response, these lens properties also implicate HIF1α as a potential requirement for lens formation and homeostasis. Here, we employed a multiomics approach combining CUT&RUN, RNAseq and ATACseq analysis to establish the genomic complement of lens HIF1α binding sites, genes activated or repressed by HIF1α and the chromatin states of HIF1α-regulated genes. Results: CUT&RUN analysis revealed 8,375 HIF1α-DNA binding complexes in the chick lens genome. 1,190 HIF1α-DNA binding complexes were significantly clustered within chromatin accessible regions (χ2 test p < 1x10-55) identified by ATACseq. Formation of the identified HIF1α-DNA complexes paralleled the activation or repression of 526 genes, 116 of which contained HIF1α binding sites within 10kB of the transcription start sites. Some of the identified HIF1α genes have previously established lens functions while others have novel functions never before examined in the lens. GO and pathway analysis of these genes implicate HIF1α in the control of a wide-variety of cellular pathways potentially critical for lens formation, structure and function including glycolysis, cell cycle regulation, chromatin remodeling, Notch and Wnt signaling, differentiation, development, and transparency. Conclusions: These data establish the first functional map of genomic HIF1α-DNA complexes in the eye lens. They identify HIF1α as an important regulator of a wide-variety of genes previously shown to be critical for lens formation and function and they reveal a requirement for HIF1α in the regulation of a wide-variety of genes not yet examined for lens function. They support a requirement for HIF1α in lens development, structure and function and they provide a basis for understanding the potential roles and requirements for HIF1α in the development, structure and function of more complex tissues.
2021-07-07 | GSE166632 | GEO
Project description:Background: During eye lens development the fetal vasculature regresses leaving the lens without a direct oxygen source. Both embryonically and throughout adult life, the lens contains a decreasing oxygen gradient from the surface to the core that parallels the natural differentiation of immature surface epithelial cells into mature core transparent fiber cells. These properties of the lens suggest a potential role for hypoxia in the regulation of genes required for mature lens structure and function. Since HIF1α is a master regulator of the hypoxic response, these lens properties also implicate HIF1α as a potential requirement for lens formation and homeostasis. Here, we employed a multiomics approach combining CUT&RUN, RNAseq and ATACseq analysis to establish the genomic complement of lens HIF1α binding sites, genes activated or repressed by HIF1α and the chromatin states of HIF1α-regulated genes. Results: CUT&RUN analysis revealed 8,375 HIF1α-DNA binding complexes in the chick lens genome. 1,190 HIF1α-DNA binding complexes were significantly clustered within chromatin accessible regions (χ2 test p < 1x10-55) identified by ATACseq. Formation of the identified HIF1α-DNA complexes paralleled the activation or repression of 526 genes, 116 of which contained HIF1α binding sites within 10kB of the transcription start sites. Some of the identified HIF1α genes have previously established lens functions while others have novel functions never before examined in the lens. GO and pathway analysis of these genes implicate HIF1α in the control of a wide-variety of cellular pathways potentially critical for lens formation, structure and function including glycolysis, cell cycle regulation, chromatin remodeling, Notch and Wnt signaling, differentiation, development, and transparency. Conclusions: These data establish the first functional map of genomic HIF1α-DNA complexes in the eye lens. They identify HIF1α as an important regulator of a wide-variety of genes previously shown to be critical for lens formation and function and they reveal a requirement for HIF1α in the regulation of a wide-variety of genes not yet examined for lens function. They support a requirement for HIF1α in lens development, structure and function and they provide a basis for understanding the potential roles and requirements for HIF1α in the development, structure and function of more complex tissues.
2021-07-07 | GSE166626 | GEO
Project description:A functional map of genomic HIF1α-DNA complexes in the eye lens revealed through multiomics analysis
| PRJNA701445 | ENA
Project description:A functional map of genomic HIF1α-DNA complexes in the eye lens revealed through multiomics analysis [CUT&RUN]
| PRJNA701440 | ENA
Project description:A functional map of genomic HIF1α-DNA complexes in the eye lens revealed through multiomics analysis [RNA-seq]
| PRJNA701449 | ENA
Project description:Mammalian SWI/SNF (mSWI/SNF or BAF) chromatin remodeling complexes play critical roles in regulating DNA accessibility and gene expression and are comprised of three final-form assemblies, cBAF, PBAF, and ncBAF, which exhibit distinct modular organization, chromatin targeting, and roles in disease. However, the contributions of each subcomplex and their constituent subunits to gene expression remain incompletely defined. Here, we performed a large-scale CRISPR-Cas9 knockout screen targeting mSWI/SNF subunits individually and in selected combinations, followed by single-cell RNA-sequencing (Perturb-seq) and SHARE-Seq. We uncover complex- and module-specific contributions across cell regulatory pathways, define paralog subunit relationships, and identify shifted functions upon perturbations. Finally, we superimpose single-cell perturbation signatures over bulk primary human tumor gene expression profiles, defining unique subunit-specific signatures and identifying tumor features that mirror BAF loss-of-function. Taken together, these data highlight the utility of large-scale single-cell genomics to uncover gene expression and chromatin accessibility signatures in human disease states.
2023-04-05 | GSE200201 | GEO
Project description:Health, disease, and mortality vary greatly at the county level, and there are strong geographical trends of disease in the United States. Healthcare is and has been a top priority for voters in the U.S., and an important political issue. Consequently, it is important to determine what relationship voting patterns have with health, disease, and mortality, as doing so may help guide appropriate policy. We performed a comprehensive analysis of the relationship between voting patterns and over 150 different public health and wellbeing variables at the county level, comparing all states, including counties in 2016 battleground states, and counties in states that flipped from majority Democrat to majority Republican from 2012 to 2016. We also investigated county-level health trends over the last 30+ years and find statistically significant relationships between a number of health measures and the voting patterns of counties in presidential elections. Collectively, these data exhibit a strong pattern: counties that voted Republican in the 2016 election had overall worse health outcomes than those that voted Democrat. We hope that this strong relationship can guide improvements in healthcare policy legislation at the county level.
| S-EPMC8294501 | biostudies-literature
Project description:Virus-microbe interactions in the ocean are commonly described by "boom and bust" dynamics, whereby a numerically dominant microorganism is lysed and replaced by a virus-resistant one. Here, we isolated a microalga strain and its infective dsDNA virus whose dynamics are characterized instead by parallel growth of both the microalga and the virus. Experimental evolution of clonal lines revealed that this viral production originates from the lysis of a minority of virus-susceptible cells, which are regenerated from resistant cells. Whole-genome sequencing demonstrated that this resistant-susceptible switch involved a large deletion on one chromosome. Mathematical modeling explained how the switch maintains stable microalga-virus population dynamics consistent with their observed growth pattern. Comparative genomics confirmed an ancient origin of this "accordion" chromosome despite a lack of sequence conservation. Together, our results show how dynamic genomic rearrangements may account for a previously overlooked coexistence mechanism in microalgae-virus interactions.
| S-EPMC7112755 | biostudies-literature
Project description:BACKGROUND: Breeders in the allo-octoploid strawberry currently make little use of molecular marker tools. As a first step of a QTL discovery project on fruit quality traits and resistance to soil-borne pathogens such as Phytophthora cactorum and Verticillium we built a genome-wide SSR linkage map for the cross Holiday x Korona. We used the previously published MADCE method to obtain full haplotype information for both of the parental cultivars, facilitating in-depth studies on their genomic organisation. RESULTS: The linkage map incorporates 508 segregating loci and represents each of the 28 chromosome pairs of octoploid strawberry, spanning an estimated length of 2050 cM. The sub-genomes are denoted according to their sequence divergence from F. vesca as revealed by marker performance. The map revealed high overall synteny between the sub-genomes, but also revealed two large inversions on LG2C and LG2D, of which the latter was confirmed using a separate mapping population. We discovered interesting breeding features within the parental cultivars by in-depth analysis of our haplotype data. The linkage map-derived homozygosity level of Holiday was similar to the pedigree-derived inbreeding level (33% and 29%, respectively). For Korona we found that the observed homozygosity level was over three times higher than expected from the pedigree (13% versus 3.6%). This could indicate selection pressure on genes that have favourable effects in homozygous states. The level of kinship between Holiday and Korona derived from our linkage map was 2.5 times higher than the pedigree-derived value. This large difference could be evidence of selection pressure enacted by strawberry breeders towards specific haplotypes. CONCLUSION: The obtained SSR linkage map provides a good base for QTL discovery. It also provides the first biologically relevant basis for the discernment and notation of sub-genomes. For the first time, we revealed genomic rearrangements that were verified in a separate mapping population. We believe that haplotype information will become increasingly important in identifying marker-trait relationships and regions that are under selection pressure within breeding material. Our attempt at providing a biological basis for the discernment of sub-genomes warrants follow-up studies to streamline the naming of the sub-genomes among different octoploid strawberry maps.
| S-EPMC3944823 | biostudies-other