RESUMO
Spin nematic is a magnetic analogue of classical liquid crystals, a fourth state of matter exhibiting characteristics of both liquid and solid1,2. Particularly intriguing is a valence-bond spin nematic3-5, in which spins are quantum entangled to form a multipolar order without breaking time-reversal symmetry, but its unambiguous experimental realization remains elusive. Here we establish a spin nematic phase in the square-lattice iridate Sr2IrO4, which approximately realizes a pseudospin one-half Heisenberg antiferromagnet in the strong spin-orbit coupling limit6-9. Upon cooling, the transition into the spin nematic phase at TC ≈ 263 K is marked by a divergence in the static spin quadrupole susceptibility extracted from our Raman spectra and concomitant emergence of a collective mode associated with the spontaneous breaking of rotational symmetries. The quadrupolar order persists in the antiferromagnetic phase below TN ≈ 230 K and becomes directly observable through its interference with the antiferromagnetic order in resonant X-ray diffraction, which allows us to uniquely determine its spatial structure. Further, we find using resonant inelastic X-ray scattering a complete breakdown of coherent magnon excitations at short-wavelength scales, suggesting a many-body quantum entanglement in the antiferromagnetic state10,11. Taken together, our results reveal a quantum order underlying the Néel antiferromagnet that is widely believed to be intimately connected to the mechanism of high-temperature superconductivity12,13.
RESUMO
Transcriptional regulation controls cellular functions through interactions between transcription factors (TFs) and their chromosomal targets. However, understanding the fate conversion potential of multiple TFs in an inducible manner remains limited. Here, we introduce iTF-seq as a method for identifying individual TFs that can alter cell fate toward specific lineages at a single-cell level. iTF-seq enables time course monitoring of transcriptome changes, and with biotinylated individual TFs, it provides a multi-omics approach to understanding the mechanisms behind TF-mediated cell fate changes. Our iTF-seq study in mouse embryonic stem cells identified multiple TFs that trigger rapid transcriptome changes indicative of differentiation within a day of induction. Moreover, cells expressing these potent TFs often show a slower cell cycle and increased cell death. Further analysis using bioChIP-seq revealed that GCM1 and OTX2 act as pioneer factors and activators by increasing gene accessibility and activating the expression of lineage specification genes during cell fate conversion. iTF-seq has utility in both mapping cell fate conversion and understanding cell fate conversion mechanisms.
Assuntos
Diferenciação Celular , Fatores de Transcrição , Animais , Camundongos , Diferenciação Celular/genética , Linhagem da Célula/genética , Perfilação da Expressão Gênica/métodos , Células-Tronco Embrionárias Murinas/metabolismo , Células-Tronco Embrionárias Murinas/citologia , Multiômica , RNA Citoplasmático Pequeno/genética , RNA Citoplasmático Pequeno/metabolismo , RNA-Seq/métodos , Análise de Sequência de RNA/métodos , Análise da Expressão Gênica de Célula Única , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , TranscriptomaRESUMO
Self-renewal and pluripotency of the embryonic stem cell (ESC) state are established and maintained by multiple regulatory networks that comprise transcription factors and epigenetic regulators. While much has been learned regarding transcription factors, the function of epigenetic regulators in these networks is less well defined. We conducted a CRISPR-Cas9-mediated loss-of-function genetic screen that identified two epigenetic regulators, TAF5L and TAF6L, components or co-activators of the GNAT-HAT complexes for the mouse ESC (mESC) state. Detailed molecular studies demonstrate that TAF5L/TAF6L transcriptionally activate c-Myc and Oct4 and their corresponding MYC and CORE regulatory networks. Besides, TAF5L/TAF6L predominantly regulate their target genes through H3K9ac deposition and c-MYC recruitment that eventually activate the MYC regulatory network for self-renewal of mESCs. Thus, our findings uncover a role of TAF5L/TAF6L in directing the MYC regulatory network that orchestrates gene expression programs to control self-renewal for the maintenance of mESC state.
Assuntos
Células-Tronco Embrionárias/metabolismo , Redes Reguladoras de Genes , Células-Tronco Pluripotentes Induzidas/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Fatores Associados à Proteína de Ligação a TATA/genética , Animais , Sistemas CRISPR-Cas , Ciclo Celular/genética , Proliferação de Células , Reprogramação Celular , Embrião de Mamíferos , Células-Tronco Embrionárias/citologia , Epigênese Genética , Fibroblastos/citologia , Fibroblastos/metabolismo , Edição de Genes , Regulação da Expressão Gênica , Células HEK293 , Histonas/genética , Histonas/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Camundongos , Cultura Primária de Células , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transdução de Sinais , Fatores Associados à Proteína de Ligação a TATA/metabolismoRESUMO
Myeloid cell heterogeneity is known, but whether it is cell-intrinsic or environmentally-directed remains unclear. Here, an inducible/reversible system pausing myeloid differentiation allowed the definition of clone-specific functions that clustered monocytes into subsets with distinctive molecular features. These subsets were orthogonal to the classical/nonclassical categorization and had inherent, restricted characteristics that did not shift under homeostasis, after irradiation, or with infectious stress. Rather, their functional fate was constrained by chromatin accessibility established at or before the granulocyte-monocyte or monocyte-dendritic progenitor level. Subsets of primary monocytes had differential ability to control distinct infectious agents in vivo. Therefore, monocytes are a heterogeneous population of functionally restricted subtypes defined by the epigenome of their progenitors that are differentially selected by physiologic challenges with limited plasticity to transition from one subset to another.
Assuntos
Granulócitos , Monócitos , Células Progenitoras Mieloides , Epigenoma , Epigênese Genética , Diferenciação Celular/genéticaRESUMO
c-Myc (Myc) is an important transcriptional regulator in embryonic stem (ES) cells, somatic cell reprogramming, and cancer. Here, we identify a Myc-centered regulatory network in ES cells by combining protein-protein and protein-DNA interaction studies and show that Myc interacts with the NuA4 complex, a regulator of ES cell identity. In combination with regulatory network information, we define three ES cell modules (Core, Polycomb, and Myc) and show that the modules are functionally separable, illustrating that the overall ES cell transcription program is composed of distinct units. With these modules as an analytical tool, we have reassessed the hypothesis linking an ES cell signature with cancer or cancer stem cells. We find that the Myc module, independent of the Core module, is active in various cancers and predicts cancer outcome. The apparent similarity of cancer and ES cell signatures reflects, in large part, the pervasive nature of Myc regulatory networks.
Assuntos
Células-Tronco Embrionárias/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Neoplasias/genética , Proteínas Proto-Oncogênicas c-myc/genética , Acetilação , Animais , Linhagem Celular , Histona Acetiltransferases/metabolismo , Histonas/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Camundongos , Fatores de Transcrição/metabolismo , Transcrição GênicaRESUMO
Recent genome-wide studies have demonstrated that pausing of RNA polymerase II (Pol II) occurred on many vertebrate genes. By genetic studies in the zebrafish tif1gamma mutant moonshine we found that loss of function of Pol II-associated factors PAF or DSIF rescued erythroid gene transcription in tif1gamma-deficient animals. Biochemical analysis established physical interactions among TIF1gamma, the blood-specific SCL transcription complex, and the positive elongation factors p-TEFb and FACT. Chromatin immunoprecipitation assays in human CD34(+) cells supported a TIF1gamma-dependent recruitment of positive elongation factors to erythroid genes to promote transcription elongation by counteracting Pol II pausing. Our study establishes a mechanism for regulating tissue cell fate and differentiation through transcription elongation.
Assuntos
Eritropoese , Fatores de Transcrição/metabolismo , Transcrição Gênica , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/embriologia , Animais , Linhagem Celular Tumoral , Células Cultivadas , Células Eritroides/metabolismo , Humanos , RNA Polimerase II/metabolismo , Peixe-Zebra/metabolismoRESUMO
The placenta is an essential organ that supports the growth and development of the fetus during pregnancy. However, cell type-specific enhancers and transcription factors (TFs), and the mechanisms underlying the maintenance and differentiation of trophoblast stem cell (TSC) populations in the human placenta remain elusive. Here, using human TSCs as a model system, we identify 31,362 enhancers that are enriched with the motifs of previously reported TSC-pivotal TFs, including TEAD4, GATA2/3 and TFAP2C. Subsequently, we identify 580 super-enhancers (SEs) and 549 SE-associated genes. These genes are robustly expressed in the human placenta and include numerous TFs, implying that SE-associated TFs (SE-TFs) may play crucial roles in placental development. Additionally, we identify the global binding sites of five TSC-pivotal SE-TFs (FOS, GATA2, MAFK, TEAD4 and TFAP2C), revealing that they preferentially co-occupy enhancers, regulate each other and form a trophoblast-active gene regulatory network. Loss-of-function studies unveil that the five TFs promote self-renewal of TSCs by activating proliferation-associated genes while repressing developmental genes. We further reveal that the five TFs exert conserved and unique functions on placental development between humans and mice. Our study provides important insights into the roles of human TSC-pivotal TFs in regulating placenta-specific gene expression programs.
Assuntos
Fatores de Transcrição , Trofoblastos , Humanos , Feminino , Gravidez , Camundongos , Animais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Placenta/metabolismo , Células-Tronco/metabolismo , Diferenciação Celular/genética , Expressão Gênica , Fatores de Transcrição de Domínio TEARESUMO
Von Hippel-Lindau (VHL) is a tumor suppressor that functions as the substrate recognition subunit of the CRL2VHL E3 complex. While substrates of VHL have been identified, its tumor suppressive role remains to be fully understood. For further determination of VHL substrates, we analyzed the physical interactome of VHL and identified the histone H3K9 methyltransferase SETBD1 as a novel target. SETDB1 undergoes oxygen-dependent hydroxylation by prolyl hydroxylase domain proteins and the CRL2VHL complex recognizes hydroxylated SETDB1 for ubiquitin-mediated degradation. Under hypoxic conditions, SETDB1 accumulates by escaping CRL2VHL activity. Loss of SETDB1 in hypoxia compared with that in normoxia escalates the production of transposable element-derived double-stranded RNAs, thereby hyperactivating the immune-inflammatory response. In addition, strong derepression of TEs in hypoxic cells lacking SETDB1 triggers DNA damage-induced death. Our collective results support a molecular mechanism of oxygen-dependent SETDB1 degradation by the CRL2VHL E3 complex and reveal a role of SETDB1 in genome stability under hypoxia.
Assuntos
Instabilidade Genômica , Histona-Lisina N-Metiltransferase , Hipóxia , Humanos , Genes Supressores de Tumor , Histona-Lisina N-Metiltransferase/metabolismo , Hipóxia/genética , Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Oxigênio/metabolismo , Ubiquitina-Proteína Ligases/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismoRESUMO
The placenta is a transient but important multifunctional organ crucial for healthy pregnancy for both mother and fetus. Nevertheless, limited access to human placenta samples and the paucity of a proper in vitro model system have hampered our understanding of the mechanisms underlying early human placental development and placenta-associated pregnancy complications. To overcome these constraints, we established a simple procedure with a short-term treatment of bone morphogenetic protein 4 (BMP4) in trophoblast stem cell culture medium (TSCM) to convert human primed pluripotent stem cells (PSCs) to trophoblast stem-like cells (TSLCs). These TSLCs show not only morphology and global gene expression profiles comparable to bona fide human trophoblast stem cells (TSCs) but also long-term self-renewal capacity with bipotency that allows the cells to differentiate into functional extravillous trophoblasts (EVT) and syncytiotrophoblasts (ST). These indicate that TSLCs are equivalent to genuine human TSCs. Our data suggest a straightforward approach to make human TSCs directly from preexisting primed PSCs and provide a valuable opportunity to study human placenta development and pathology from patients with placenta-related diseases.
Assuntos
Placentação , Células-Tronco Pluripotentes , Trofoblastos , Biomarcadores , Proteína Morfogenética Óssea 4 , Diferenciação Celular , Feminino , Humanos , Modelos Biológicos , Placenta , Gravidez , Trofoblastos/metabolismoRESUMO
We reveal the critical effect of ultrashort dephasing on the polarization of high harmonic generation in Dirac fermions. As the elliptically polarized laser pulse falls in or slightly beyond the multiphoton regime, the elliptically polarized high harmonic generation is produced and exhibits a characteristic polarimetry of the polarization ellipse, which is found to depend on the decoherence time T2. T2 could then be determined to be a few femtoseconds directly from the experimentally observed polarimetry of high harmonics. This shows a sharp contrast with the semimetal regime of higher pump intensity, where the polarimetry is irrelevant to T2. An access to the dephasing dynamics would extend the prospect of high harmonic generation into the metrology of a femtosecond dynamic process in the coherent quantum control.
RESUMO
Spatial learning and memory flexibility are known to require long-term potentiation (LTP) and long-term depression (LTD), respectively, on a cellular basis. We previously showed that cyclin Y (CCNY), a synapse-remodeling cyclin, is a novel actin-binding protein and an inhibitory regulator of functional and structural LTP in vitro. In this study, we report that Ccny knockout (KO) mice exhibit enhanced LTP and weak LTD at Schaffer collateral-CA1 synapses in the hippocampus. In accordance with enhanced LTP, Ccny KO mice showed improved spatial learning and memory. However, although previous studies reported that normal LTD is necessary for memory flexibility, Ccny KO mice intriguingly showed improved memory flexibility, suggesting that weak LTD could exert memory flexibility when combined with enhanced LTP. At the molecular level, CCNY modulated spatial learning and memory flexibility by distinctively affecting the cofilin-actin signaling pathway in the hippocampus. Specifically, CCNY inhibited cofilin activation by original learning, but reversed such inhibition by reversal learning. Furthermore, viral-mediated overexpression of a phosphomimetic cofilin-S3E in hippocampal CA1 regions enhanced LTP, weakened LTD, and improved spatial learning and memory flexibility, thus mirroring the phenotype of Ccny KO mice. In contrast, the overexpression of a non-phosphorylatable cofilin-S3A in hippocampal CA1 regions of Ccny KO mice reversed the synaptic plasticity, spatial learning, and memory flexibility phenotypes observed in Ccny KO mice. Altogether, our findings demonstrate that LTP and LTD cooperatively regulate memory flexibility. Moreover, CCNY suppresses LTP while facilitating LTD in the hippocampus and negatively regulates spatial learning and memory flexibility through the control of cofilin-actin signaling, proposing CCNY as a learning regulator modulating both memorizing and forgetting processes.
Assuntos
Actinas , Aprendizagem Espacial , Camundongos , Animais , Hipocampo/metabolismo , Potenciação de Longa Duração/fisiologia , Plasticidade Neuronal/fisiologia , Sinapses/metabolismo , Camundongos Knockout , Ciclinas/genética , Ciclinas/metabolismo , Fatores de Despolimerização de Actina/metabolismoRESUMO
A family of pyrazinone metabolites (1-11) were characterized from Staphylococcus xylosus ATCC 29971. Six of them were hydroxylated or methoxylated, which were proposed to be produced by the rare noncatalytic oxa-Michael addition reaction with a water or methanol molecule. It was confirmed that isopropyl alcohol can also be the Michael donor of the reaction. 1-7 and the synthetic precursor 2a showed significant inhibition of breast cancer cell migration.
Assuntos
Pirazinas , Staphylococcus , Humanos , Movimento Celular/efeitos dos fármacos , Estrutura Molecular , Pirazinas/química , Pirazinas/farmacologia , Staphylococcus/efeitos dos fármacosRESUMO
Polycyclic aromatic hydrocarbons (PAHs), notably benzo[a]pyrene (BaP), are environmental contaminants with multiple adverse ecological implications. Numerous studies have suggested the use of BaP biodegradation using various bacterial strains to remove BaP from the environment. This study investigates the BaP biodegradation capability of Pigmentiphaga kullae strain KIT-003, isolated from the Nak-dong River (South Korea) under specific environmental conditions. The optimum conditions of biodegradation were found to be pH 7.0, 35°C, and a salinity of 0â¯%. GC-MS analysis suggested alternative pathways by which KIT-003 produced catechol from BaP through several intermediate metabolites, including 4-formylchrysene-5-carboxylic acid, 5,6-dihydro-5,6-dihydroxychrysene-5-carboxylic acid (isomer: 3,4-dihydro-3,4-dihydroxychrysene-4-carboxylic acid), naphthalene-1,2-dicarboxylic acid, and 2-hydroxy-1-naphthoic acid. Proteomic profiles indicated upregulation of enzymes associated with aromatic compound degradation, such as nahAc and nahB, and of those integral to the tricarboxylic acid cycle, reflecting the strain's adaptability to and degradation of BaP. Lipidomic analysis of KIT-003 demonstrated that BaP exposure induced an accumulation of glycerolipids such as diacylglycerol and triacylglycerol, indicating their crucial role in bacterial adaptation mechanisms under BaP stress. This study provides significant scientific knowledge regarding the intricate mechanisms involved in BaP degradation by microorganisms.
Assuntos
Benzo(a)pireno , Biodegradação Ambiental , Benzo(a)pireno/metabolismo , Benzo(a)pireno/toxicidade , República da Coreia , Proteômica , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade , Cromatografia Gasosa-Espectrometria de Massas , Catecóis/metabolismo , Rios/química , Rios/microbiologia , MultiômicaRESUMO
Embodying bosonic and interactive characteristics in two-dimensional space, excitons in transition metal dichalcogenides (TMDCs) have garnered considerable attention. The utilization of the strong-correlation effects, long-range transport, and valley-dependent properties requires customizing exciton decay dynamics. Vacuum-field manipulation allows radiative decay engineering without disturbing intrinsic material properties. However, conventional flat mirrors cannot customize the radiative decay landscape in TMDC's plane or support vacuum-field interference with desired spectrum and polarization properties. Here, we present a meta-mirror platform resolving the issues with more optical degrees of freedom. For neutral excitons of the monolayer MoSe2, the optical layout formed by meta-mirrors manipulated the radiative decay rate in space by 2 orders of magnitude and revealed the statistical correlation between emission intensity and spectral line width. Moreover, the anisotropic meta-mirror demonstrated polarization-dependent radiative decay control. Our platform would be promising to tailor two-dimensional distributions of lifetime, density, diffusion, and polarization of TMDC excitons in advanced opto-excitonic applications.
RESUMO
Color matching experiments were conducted for 11 pairs of displays, using 7 displays with different spectral characteristics. The color matching results between the LCD display and displays that have a narrowband spectrum, such as a laser projector, QLED, or OLED, demonstrated a significant color difference between two matched colors. The maximum difference was 18.52 ΔE00, which indicates the white color difference between the LCD and laser projector. There was also a clear observer variability of 2.27 ΔE00. The new cone fundamental function derived from 757 metameric pairs showed good performance compared to CIE standard observers reducing the display color mismatching significantly. This function also demonstrated a better performance when evaluating color matching in color chart image.
RESUMO
Much attention has focused on a small set of transcription factors that maintain human or mouse embryonic stem (ES) cells in a pluripotent state. To gain a more complete understanding of the regulatory network that maintains this state, we identified target promoters of nine transcription factors, including somatic cell reprogramming factors (Oct4, Sox2, Klf4, and c-Myc) and others (Nanog, Dax1, Rex1, Zpf281, and Nac1), on a global scale in mouse ES cells. We found that target genes fall into two classes: promoters bound by few factors tend to be inactive or repressed, whereas promoters bound by more than four factors are largely active in the pluripotent state and become repressed upon differentiation. Furthermore, we propose a transcriptional hierarchy for reprogramming factors and broadly distinguish targets of c-Myc versus other factors. Our data provide a resource for exploration of the complex network maintaining pluripotency.
Assuntos
Células-Tronco Embrionárias/metabolismo , Redes Reguladoras de Genes , Células-Tronco Pluripotentes/metabolismo , Fatores de Transcrição/metabolismo , Animais , Imunoprecipitação da Cromatina , Código das Histonas , Humanos , Fator 4 Semelhante a Kruppel , Camundongos , Dados de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Regiões Promotoras GenéticasRESUMO
Recent genomic data analyses have revealed important underlying logics in eukaryotic gene regulation, such as CpG islands (CGIs)-dependent dual-mode gene regulation. In mammals, genes lacking CGIs at their promoters are generally regulated by interconversion between euchromatin and heterochromatin, while genes associated with CGIs constitutively remain as euchromatin. Whether a similar mode of gene regulation exists in non-mammalian species has been unknown. Here, through comparative epigenomic analyses, we demonstrate that the dual-mode gene regulation program is common in various eukaryotes, even in the species lacking CGIs. In cases of vertebrates or plants, we find that genes associated with high methylation level promoters are inactivated by forming heterochromatin and expressed in a context-dependent manner. In contrast, the genes with low methylation level promoters are broadly expressed and remain as euchromatin even when repressed by Polycomb proteins. Furthermore, we show that invertebrate animals lacking DNA methylation, such as fruit flies and nematodes, also have divergence in gene types: some genes are regulated by Polycomb proteins, while others are regulated by heterochromatin formation. Altogether, our study establishes gene type divergence and the resulting dual-mode gene regulation as fundamental features shared in a broad range of higher eukaryotic species.
Assuntos
Regulação da Expressão Gênica , Animais , Caenorhabditis elegans/genética , Ilhas de CpG , Metilação de DNA , Drosophila melanogaster/genética , Epigênese Genética , Regulação da Expressão Gênica de Plantas , Regiões Promotoras Genéticas , Transcrição Gênica , Vertebrados/genéticaRESUMO
Gut microbes play diverse roles in modulating host fitness, including longevity; however, the molecular mechanisms underlying their mediation of longevity remain poorly understood. We performed genome-wide screens using 3,792 Escherichia coli mutants and identified 44 E. coli mutants that modulated Caenorhabditis elegans longevity. Three of these mutants modulated C. elegans longevity via the bacterial metabolite methylglyoxal (MG). Importantly, we found that low MG-producing E. coli mutants, Δhns E. coli, extended the lifespan of C. elegans through activation of the DAF-16/FOXO family transcription factor and the mitochondrial unfolded protein response (UPRmt). Interestingly, the lifespan modulation by Δhns did not require insulin/insulin-like growth factor 1 signaling (IIS) but did require TORC2/SGK-1 signaling. Transcriptome analysis revealed that Δhns E. coli activated novel class 3 DAF-16 target genes that were distinct from those regulated by IIS. Taken together, our data suggest that bacteria-derived MG modulates host longevity through regulation of the host signaling pathways rather than through nonspecific damage on biomolecules known as advanced glycation end products. Finally, we demonstrate that MG enhances the phosphorylation of hSGK1 and accelerates cellular senescence in human dermal fibroblasts, suggesting the conserved role of MG in controlling longevity across species. Together, our studies demonstrate that bacteria-derived MG is a novel therapeutic target for aging and aging-associated pathophysiology.
Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans , Fatores de Transcrição Forkhead/metabolismo , Longevidade/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Aldeído Pirúvico , Animais , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/microbiologia , Escherichia coli/metabolismo , Microbioma Gastrointestinal/fisiologia , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Modelos Biológicos , Aldeído Pirúvico/metabolismo , Aldeído Pirúvico/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transcriptoma/genéticaRESUMO
Balsamisides A-D (1-4) are anti-inflammatory and neurotrophic biflavonoidal glycosides originally proposed to possess an epoxide functionality at the C-2/C-3 position. However, there are inconsistencies in their 13C NMR chemical shift values with those of previously reported analogs, indicating that reanalysis of NMR data for structures of 1-4 is necessary. Computational methods aided by the DP4+ probability technique and ECD calculations enabled structural reassignment of 1-4 to have a 2,3-dihydro-3-hydroxyfuran (3-DHF) instead of an epoxide. Additionally, two new biflavonoidal glycosides, balsamisides E and F (14 and 18), possessing a 2,3-dihydro-2-hydroxyfuran (2-DHF) and a 1,4-dioxane ring, respectively, were characterized by conventional NMR and MS data analysis as well as DP4+ and ECD methods. Systematic 13C NMR analysis was performed on the four aforementioned classes of biflavonoids with a 2- or 3-DHF, epoxide, or 1,4-dioxane. As a result, diagnostic 13C NMR chemical shift values of C-2/C-3 for rapid determination of these four biflavonoid classes were formulated, and based on this first empirical rule for (bi)flavonoids eight previously reported ones were structurally revised.
Assuntos
Biflavonoides , Biflavonoides/química , Compostos de Epóxi , Flavonoides/química , Glicosídeos/química , Estrutura MolecularRESUMO
Self-renewal and pluripotency of embryonic stem cells (ESCs) are established by multiple regulatory pathways operating at several levels. The roles of histone demethylases (HDMs) in these programs are incompletely defined. We conducted a functional RNAi screen for HDMs and identified five potential HDMs essential for mouse ESC identity. In-depth analyses demonstrate that the closely related HDMs Jmjd2b and Jmjd2c are necessary for self-renewal of ESCs and induced pluripotent stem cell generation. Genome-wide occupancy studies reveal that Jmjd2b unique, Jmjd2c unique, and Jmjd2b-Jmjd2c common target sites belong to functionally separable Core, Polycomb repressive complex (PRC), and Myc regulatory modules, respectively. Jmjd2b and Nanog act through an interconnected regulatory loop, whereas Jmjd2c assists PRC2 in transcriptional repression. Thus, two HDMs of the same subclass exhibit distinct and combinatorial functions in control of the ESC state. Such complexity of HDM function reveals an aspect of multilayered transcriptional control.