Genomes are organized into high-level 3-dimensional structures, and DNA elements separated by long genomic distances could functionally interact. Many transcription factors bind to regulatory DNA elements distant from gene promoters. While distal binding sites have been shown to regulate transcription by long-range chromatin interactions at a few loci, chromatin interactions and their impact on transcription regulation have not been investigated in a genome-wide manner. Therefore, we developed Chromatin Interaction Analysis by Paired-End Tag sequencing (ChIA-PET) for de novo detection of global chromatin interactions, and comprehensively mapped the chromatin interaction network bound by oestrogen receptor α (ERα) in the human genome. We found that most high-confidence remote ERα binding sites are anchored at gene promoters through long-range chromatin interactions, suggesting that ERα functions by extensive chromatin looping to bring genes together for coordinated transcriptional regulation. We propose that chromatin interactions constitute a primary mechanism for regulating transcription in mammalian genomes.
Multi-resonance TADF (MR-TADF) emitters are promising for high-resolution OLEDs, but the concurrent optimization of excited-state dynamics and color purity remains a tough challenge. Herein, three deep-blue MR-TADF compounds (BN1-BN3) featuring gradually enlarged ring-fused structures and increased rigidity are accessed by lithiumfree borylation in high yields from the same precursor, with all the emitters possessing CIE y coordinates below 0.08. Structure-property investigations demonstrate a strategic improvement of the oscillator strength (f osc ) and acceleration of the reverse intersystem crossing (RISC) process by extending the π-skeleton, where BN3 realizes a maximum external quantum efficiency (EQE) of 37.6 % and reduced roll-off, thus showing the best efficiency reported for deep-blue TADF OLEDs. The internal regulation of the efficiency and color purity of these compounds validate the general effectiveness to achieve advanced deep-blue narrowband emitters with higher-order boron/nitrogen-based MR motifs.
Estrogens, such as 17-estradiol (E 2 ), 3 are pleiotropic hormones whose effects are responsible for many physiological processes, including normal growth, development, and the precise and coordinated regulation of gene expression in tissues of the reproductive tract, central nervous system, and bone (1, 2).Estrogens also have important functions in hormone-dependent diseases, such as breast cancer and osteoporosis (1, 2). Selective estrogen receptor modulators, therapeutic agents that act as agonists or antagonists depending on the target tissue, are currently used in the treatment and prevention of these and other hormone-related disorders (1-3). Estrogens and selective estrogen receptor modulators exert their effects through two estrogen receptors (ERs), ER alpha (ER␣/ESR1/NR3A1) and ER beta (ER/ESR2/NR3A2), which belong to a large superfamily of nuclear hormone receptor proteins (2, 3). ERs share a conserved structural and functional organization with other members of the nuclear hormone receptor superfamily, including domains responsible for ligand binding, dimerization, DNA binding, and transcriptional activation (2, 3).As their domain structures imply, ERs behave as ligand-inducible, DNA binding transcription factors (2, 3). Their transcriptional activities require the recruitment of a variety of coregulatory proteins by the receptors to estrogen-regulated promoters through either direct or indirect interactions (2, 3). A group of factors, including the p160/steroid receptor co-activator (SRC) family of proteins and the Mediator-like complexes (e.g. TRAP, DRIP, and ARC), have been shown to interact with and stimulate the transcriptional activities of ERs by interacting directly with the ligand binding domain in a ligand and activation function-2-dependent manner (2, 3). Other factors that contain enzymatic activities, such as the histone acetyltransferase p300/CBP and the histone methyltransferase CARM-1, are recruited indirectly by ERs mainly via interactions with the SRC proteins (2, 3). A smaller subset of ER-interacting factors has been shown to bind primarily to the N-terminal A/B region of the receptors, including the RNA-binding protein p68/p72 and SRA (2, 3). Together, these co-regulatory proteins are recruited by ERs in a precise temporal and coordinated manner in response to estrogen to promote local changes in histone modifications, chromatin structure, and the recruitment of RNA polymerase II to the promoters of target genes.Numerous estrogen target genes have been identified through expression microarray studies (reviewed in Ref. 4); however, it is unclear what fraction of these genes are directly regulated by ERs. Direct regulation by estrogen is largely due to the recruitment of ERs to genomic regions containing sequence specific cis-regulatory motifs (2, 3). These sequences mostly
Piezochromic fluorescent (PCF) materials with distinct multicolor switching have attracted wide attention in many fields such as optoelectronic devices and deformation detection. However, few PCF materials with low-pressure stimuli and good recoverability have been reported. A highly sensitive and easily recoverable PCF molecular system that can switch between green (G) and orange (O) emissions upon an extremely low piezoresponsive (PR) of 0.5 MPa and heating at 120 °C is demonstrated. A mechanistic study combining X-ray diffraction analysis and the theoretical calculations reveal that a slight change in slipping-angle of π-stacks induced by mechanical pressure amplifies the exciton couplings from G to O J-aggregates, leading to not only distinct PCF switching but also high emission efficiencies >0.5 owing to superradiance of J-aggregate excitons. Benefiting from low MPa PR, high emission efficiency, and good recoverability applications including haptic sensors and anti-counterfeiting application are demonstrated. This research introduces the effect of stimuli-responsive excitonic coupling as new design guidance for developing PCF materials with low-pressure stimuli, high emission efficiency, and good recoverability.
Obesity induces profound transcriptome changes in adipocytes, and recent evidence suggests that long-noncoding RNAs (lncRNAs) play key roles in this process. We performed a comprehensive transcriptome study by RNA sequencing in adipocytes isolated from interscapular brown, inguinal, and epididymal white adipose tissue in diet-induced obese mice. The analysis revealed a set of obesity-dysregulated lncRNAs, many of which exhibit dynamic changes in the fed versus fasted state, potentially serving as novel molecular markers of adipose energy status. Among the most prominent lncRNAs is , which is transcribed from an enhancer region upstream of leptin (). Expression of is sensitive to insulin and closely correlates to expression across diverse pathophysiological conditions. Functionally, induction of is essential for adipogenesis, and its presence is required for the maintenance of expression in vitro and in vivo. Direct interaction was detected between DNA loci of and in mature adipocytes, which diminished upon knockdown. Our study establishes as a new regulator of .
Stimuli-responsive functional luminescent materials with tunable color and long-persistent emission have emerged as a powerful tool in information encryption, anticounterfeiting, and bioelectronics. Herein, we prove a novel strategy for manipulating the proton transfer pathways in the salicylaldehyde derivative EQCN solutions/powder to produce excitation wavelength-dependent (Ex-De) performances with switchable emissions (blue-sky, green, and orange). The experiments and theoretical results demonstrated that the different luminous colors are originated from enol (E) form (blue-sky), Keto-1 (K1) form (orange) through the excited-state intramolecular proton transfer (ESIPT) process, and Keto-2 (K2) form (green) through the excited-state longrange proton transfer (ESLRPT) process. We leverage synergistic effects between the dopant and matrix (dimethyl terephthalate, DTT) to manipulate the excited-state proton transfer pathway in EQCN@DTT mixture powders to generate Ex-De long-persistent luminescence (Ex-De-LPL), which can be well applied in multilevel information encryption. This strategy not only paves an intriguing way for the construction and preparation of pure organic Ex-De materials but also offers a guideline for developing LPL materials based on ESLRPT processes.
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