Non-preferential localization of poly (ADP-ribose) polymerase activity in transcriptionally active chromatin.
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Animals↗
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Results for “Transcriptional Activation”
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Bimodal retrograde signaling disrupts a suppressor network and activates a key transcriptional activator to direct stress responses.
Plastid-to-nucleus communication, crucial for regulating stress-responsive gene expression, has long intrigued researchers. This study reveals how the plastidial metabolite 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate (MEcPP) orchestrates transcriptional reprogramming by modulating the rapid stress response element (RSRE), a conserved regulatory hub in the plant general stress response network. Yeast one-hybrid assays identified HAT1, a class II HD-Zip protein, as a negative regulator of RSRE. Genetic analyses, including HAT1 overexpression and knockdowns, confirmed its role in suppressing RSRE activity. Interaction assays uncovered a suppression network involving HAT1, the co-repressor TOPLESS (TPL), and the nuclear importin IMPα-9. Furthermore, HAT1 interacts with calmodulin-binding transcription activator 3 (CAMTA3), a calcium/calmodulin-binding transcription factor known to activate RSRE. AlphaFold modeling provided insights into the architecture of the HAT1-RSRE complex and HAT-CAMTA3 interaction, supported by conserved domains across plant species. Under stress condition, MEcPP accumulation promotes the 26S proteasomal degradation of TPL and IMPα-9 while reduces auxin-dependent HAT1 expression. Additionally, MEcPP enhances Ca2+ influx, activating CAMTA3 and enabling it to bind RSRE, thereby initiating the transcription of stress response genes. This dual mechanism-dismantling suppressors (HAT1, TPL, and IMPα-9) and activating CAMTA3-underscores MEcPP's central role in plastid-to-nucleus signaling. These findings emphasize MEcPP's pivotal function in dynamically regulating gene expression to maintain cellular homeostasis under environmental stress.
Arabidopsis Proteins↗
An IRAK1-snRNA axis activates ATM to promote accurate repair within transcriptionally active chromatin.
Genomic integrity in transcriptionally active regions is pivotal for suppressing oncogenic mutations, yet the mechanisms that govern precise homologous recombination (HR) repair within these regions remain elusive. Here, we report that the IRAK1-spliceosome axis operates with small nuclear RNA (snRNA) as a central hub, potently promoting accurate repair at DNA double-strand break (DSB) sites within active chromatin in human cancer cells. Mechanistically, IRAK1 phosphorylates spliceosomal serine/arginine (SR)-rich proteins to recruit snRNA to DSBs, inducing robust condensation of the MRE11-RAD50-NBS1 (MRN) complex near transcriptionally active regions to create an ATM activation platform. Collectively, our findings define a prevalent mechanism governing region-specific precise repair in transcriptionally active domains, where snRNA acts as a "transcription repair bridge" to link transcriptional processes to HR repair and ultimately preserves genomic stability. Inhibiting IRAK1 axis impairs HR repair in transcriptionally active regions, causing a marked increase in mutation rates specific to these regions and cancer-cell chemosensitivity.
Humans↗
A contextual activity score (CAS) for inferring ADAR-associated transcriptional activity across RNA-seq, single-cell, and spatial transcriptomics.
BACKGROUND AND OBJECTIVE: Adenosine-to-inosine RNA editing, catalyzed by Adenosine Deaminases Acting on RNA (ADARs), is a widespread modification involved in neural function, immune regulation, and cancer. The Alu Editing Index (AEI) is the standard metric to estimate ADAR activity but requires raw sequencing reads and is poorly suited for single-cell and spatial transcriptomic data. This study aimed to develop an alternative framework for inferring ADAR-associated transcriptional activity from gene expression data across diverse transcriptomic technologies. METHODS: We developed the Contextual Activity Score (CAS), a framework based on transcriptional signatures from ADAR perturbation experiments. Context-specific signatures were generated for human neurons, mouse neurons, and cancer models to infer ADAR1 and ADAR2 activity. CAS was computed from normalized gene expression matrices using regulon-based enrichment analysis. Performance was evaluated by comparing with the Alu Editing Index across bulk RNA sequencing datasets, simulated sequencing depths, and library preparation protocols. RESULTS: CAS showed strong concordance with the Alu Editing Index across multiple datasets, while remaining robust to reduced sequencing depth and different library protocols. Unlike the Alu Editing Index, CAS can be applied to single-cell and spatial transcriptomic data and enables the independent assessment of ADAR2 activity. In cancer and neuronal contexts, CAS captured biologically meaningful variations in ADAR-associated transcriptional activity at sample, cell-type, and spatial levels. CONCLUSION: CAS provides a scalable approach applicable across multiple RNA-seq protocols for estimating ADAR-associated transcriptional activity using gene expression data. This method, implemented in an open-source R package for broad adoption, expands the ability to study ADAR-associated transcriptional activity across transcriptomic modalities where direct editing quantification is challenging, such as single-cell and spatial transcriptomics.
Adenosine Deaminase↗
Characterization of active transcription units in Balbiani rings of Chironomus tentans.
Specific active transcription units on chromosome IV in the salivary glands of Chironomus tentans have been visualized by the Miller spreading technique and in situ by conventional electron microscopy. These units are likely to be located in the two most conspicuous puffs on chromosome IV, Balbiani ring 1 (BR 1) and Balbiani ring 2 (BR 2). The transcription units in these Balbiani rings generate 75S RNA molecules constituting putative messenger RNA species for the predominant cellular product, the salivary polypeptides. Solitary active transcription units with a mean length of 7.7 micron were observed most frequently. The lateral ribonucleoprotein (RNP) fibers of each unit formed a single length gradient. The number of fibers per unit was 123 (+/- 24), or about 16 growing RNP fibers per micron of chromosome fiber. The considerable variation in the number of RNP fibers per unit suggests that transcription can be modulated at the level of the individual gene. The modulation is probably achieved via the initiation event and/or via an early pretermination step, but a change in the elongation rate could not be excluded. The number of polymerases starting to traverse the whole gene was estimated to be six per min and transcription unit, and the rate of RNA chain elongation was calculated to be 31 nucleotides per second at 18 degrees C. The properties of the chromosome fiber within the active 75S RNA units and also within their vicinity were studied in the Miller spreads. The inactive chromosome fiber exhibited a uniform beaded conformation, while the active fiber was sparsely and irregularly beaded. Furthermore, the chromosome fiber was more extended in the active 75S RNA unit than in inactive regions (DNA packing ratios of 1.6 and 1.9, respectively). By comparing the properties of the active 75S RNA gene with those of active genes in other systems, it was inferred that the loss of beads and the extension of the fiber in the active unit is probably directly related to the level of transcriptive activity. Finally, a smooth nonbeaded segment of 0.18 micron in length was found to precede the RNP fiber gradient. This segment may have a role in the process of transcriptional regulation. On the basis of comparison with the active transcription units in spread preparations. It was possible to identify active units in the Balbiani rings in sectioned material using conventional electron microscopy. In both BR 1 and BR 2 an active unit appeared as a loop, consisting of a fiber axis and having RNP granules attached to the loop axis by stalks. The growing RNP fibers therefore seem to be organized into granular structures during the transcription process, and the final products in BR 1 and BR2 are granules, 500 A in diameter, each containing a 75S RNA molecule.
Animals↗
Transcriptionally active and inactive regions of nucleolar chromatin in amplified nucleoli of fully grown oocytes of hibernating frogs, Rana pipiens (Amphibia, Anura). A quantitative electron microscopic study.
Chromatin structures contained in nuclei of full-grown oocytes of hibernating northern leopard frogs, Rana pipiens, kept at 4 degrees C were examined by light and electron microscopy, with special emphasis on the morphology of spread nucleoli. Light microscopic inspection of the in situ arrangement revealed that at this stage of oogenesis the numerous amplified nucleoli, together with the chromosomes, were included in a centrally located aggregate. Characteristically, the nucleoli appeared spheroidal and showed large size differences; many of them revealed a caveolated interior and close association with large dense bodies of granular (GDB) or fibrillar (FDB) substructure. A spreading procedure involving limited dispersal of nucleolar chromatin allowed the analysis of a large number of individual nucleoli from a specific nucleus. Electron microscopy showed that different types of nucleoli which could be distinguished in terms of transcriptional activity occurred in the same nucleus: (i) Nucleoli in which nearly all pre-rRNA gene regions appeared as fully covered by lateral fibrils, indicative of active transcription ('active nucleoli'); (ii) nucleoli that contained exclusively or predominantly chromatin strands free of lateral fibrils and were characterized by a uniformly beaded appearance, interpreted as transcriptionally inactive, nucleosome-packed chromatin ('inactive nucleoli'); and (iii) nucleoli in which a number of typical arrays of lateral fibril gradients occurred besides other regions that were free of such fibrils and apparently non-transcribed ('partly inactive nucleoli'). Quantitative evaluations of the proportions of active and inactive nucleolar chromatin indicated that a minimum of 70% of nucleolar DNA is not transcribed at this stage of oogenesis. Details of the pattern and ultrastructural organization of active and inactive chromatin regions are presented. Lampbrush chromosome structures were observed in the same nuclei and also showed transcriptional structures, though often with reduced packing density of lateral fibrils. The observations show that a number of genes of both kinds, those coding for pre-rRNAs and those coding for proteins, are transcribed in full-grown oocytes of hibernating frogs at 4 degrees C. However, the data also indicate that the number of transcribed genes and the frequency of transcriptional events are greatly reduced at this stage of oogenesis, especially in the nucleolar chromatin.
Animals↗
Reporter Gene Assays to Measure FOXO-Specific Transcriptional Activity.
The forkhead box O (FOXO) family of transcription factors translates environmental cues into precise gene expression patterns maintaining cellular equilibrium while influencing critical determinations of cell destiny and differentiation. FOXO proteins exert their effects through specific consensus binding to promoter sites within target genes. Notably, among the array of techniques available for assessing the transcriptional activity of FOXO factors, the utilization of luciferase-based reporters emerges as particularly distinctive. Luciferase, an enzyme sourced from bioluminescent organisms, instigates the oxidation of luciferin, culminating in the generation of oxyluciferin accompanied by discernible luminescence, a quantifiable event readily gauged using a luminometer. The adoption of luciferase activity as a measure in transcriptional assays is widespread due to its numerous advantages including simplicity, remarkable reproducibility, and high sensitivity. Moreover, the continuous advancements witnessed in luciferase-based vectors and measurement reagents bestow notable flexibility upon this methodology. Luciferase-based reporters offer a powerful tool for uncovering constituents within the signaling pathways governing FOXO factor function. Furthermore, these assays are also suitable for evaluating the efficacy of FOXO-targeting agents, whether they be inhibitors or activators. Here, we present a comprehensive, step-by-step elucidation of a commonly employed assay, adeptly quantifying the potential of small molecular compounds to amplify FOXO-specific transcriptional activity in U2OS cells.
Genes, Reporter↗
Isolation of a transcriptionally active chromosome from chloroplasts of Euglena gracilis.
A transcriptionally active chromosome has been isolated in highly purified form from choroplasts of Euglena gracilis, It contains chloroplast DNA, DNA-dependent RNA polymerase, and other proteins. Transcription occurs at low levels of endogenous DNA, and is indifferent to high levels of exogenous DNA. RNA chain elongation continues for several hours in vitro, and RNA chain initiation, determined by [gamma-32P]ATP incorporation, is continuous for at least 1 h in vitro. Maximal rates for RNA synthesis require only a divalent cation and the four ribonucleoside triphosphates. Apparent Km values for adenosine triphosphate, cytidine triphosphate, guanosine triphosphate, and uridine triphosphate are 4.0, 0.6, 2.5, and 2.3 muM, respectively. As would be expected for a DNA-dependent RNA polymerase, RNA synthesis is inhibited by actinomycin D. However, rifampicin and streptolydigin, inhibitors of procaryotic RNA synthesis, and alpha-amanitin, an inhibitor of eucaryotic nuclear RNA polymerases II and III, do not inhibt the RNA synthesis reaction. Heparin, which is a potent inhibitor of the initiation of RNA synthesis by a nontemplate bound RNA polymerase, also does not inhibit RNA synthesis. Isolation of transcriptionally active chromosomes should prove to be a useful method to study the mechanism of selective RNA transcription of eucaryotic chromosomes.
Aminoglycosides↗
SUMO modification of the Ets-related transcription factor ERM inhibits its transcriptional activity.
A variety of transcription factors are post-translationally modified by SUMO, a 97-residue ubiquitin-like protein bound covalently to the targeted lysine. Here we describe SUMO modification of the Ets family member ERM at positions 89, 263, 293, and 350. To investigate how SUMO modification affects the function of ERM, Ets-responsive intercellular adhesion molecule 1 (ICAM-1) and E74 reporter plasmids were employed to demonstrate that SUMO modification causes inhibition of ERM-dependent transcription without affecting the subcellular localization, stability, or DNA-binding capacity of the protein. When the adenoviral protein Gam1 or the SUMO protease SENP1 was used to inhibit the SUMO modification pathway, ERM-dependent transcription was de-repressed. These results demonstrate that ERM is subject to SUMO modification and that this post-translational modification causes inhibition of transcription-enhancing activity.
Adenoviridae↗
Nonpromoter methylation of the CDKN2A gene with active transcription is associated with improved locoregional control in laryngeal squamous cell carcinoma.
We previously reported a novel association between CDKN2A nonpromoter methylation and transcription (ARF/INK4a) in human papillomavirus associated oropharyngeal tumors. In this study we assessed whether nonpromoter CDKN2A methylation in laryngeal squamous cell carcinomas (LXSCC) conferred a similar association with transcription that predicted patient outcome. We compared DNA methylation and ARF/INK4a RNA expression levels for the CDKN2A locus using the Illumina HumanMethylation27 beadchip and RT-PCR in 43 LXSCC tumor samples collected from a prospective study of head and neck cancer patients treated at Montefiore Medical Center (MMC). Validation was performed using RNAseq data on 111 LXSCC tumor samples from the Cancer Genome Atlas (TCGA). The clinical relevance of combined nonpromoter CDKN2A methylation and transcription was assessed by multivariate Cox regression for locoregional recurrence on a subset of 69 LXSCC patients with complete clinicopathologic data from the MMC and TCGA cohorts. We found evidence of CDKN2A nonpromoter hypermethylation in a third of LXSCC from our MMC cohort, which was significantly associated with increased ARF and INK4a RNA expression (Wilcoxon rank-sum, P = 0.007 and 0.003, respectively). A similar association was confirmed in TCGA samples (Wilcoxon rank-sum test P < 0.0001 for ARF and INK4a). Patients with CDKN2A hypermethylation or high ARF/INK4a expression were significantly less likely to develop a locoregional recurrence compared to those with neither of the features, independent of other clinicopatholgic risk factors (adjusted hazard ratio=0.21, 95% confidence interval:0.05-0.81). These results support the conclusion that CDKN2A nonpromoter methylation is associated with increased ARF and INK4a RNA expression, and improved locoregional control in LXSCC.
Carcinoma, Squamous Cell↗
HP1α binding creates a local barrier against transcription activation and persists during chromatin decondensation.
Mouse pericentric heterochromatin forms compacted, transcriptionally silent domains, termed chromocenters, that are enriched in heterochromatin protein 1 (HP1). Whether HP1α represses chromocenters by binding locally or by maintaining a phase-separated compartment is unresolved. We investigated this question by recruiting transcriptional activators to mouse fibroblast chromocenters and quantifying repression at a transcription reporter. HP1α established a promoter-proximal barrier that suppressed weaker activators (VP16) but was overcome by stronger ones (VP64-p65-Rta [VPR] and p65). Activator-induced decondensation and transcription occurred without displacing HP1α or H3K9 trimethylation, and HP1α retained its granular distribution and stoichiometric binding dynamics. Multi-color super-resolution imaging revealed spatial segregation of transcribed and HP1α-bound regions at the nanodomain scale. A nanodomain model captured how repeat clusters independently transition between silenced and activated states. These data establish that HP1α and H3K9me3 act through independently switchable nanodomains, accounting for chromocenter regulation without invoking phase separation.
Animals↗
Comparative organization of active transcription units in Oncopeltus fasciatus.
We have analyzed electron micrographs of chromatin-associated fiber arrays from embryos of the milkweed bug, Oncopeltus fasciatus. The analysis has revealed that the arrays have highly ordered patterns of fiber spacings and lengths. These patterns support the interpretation that the fibers are nascent RNA with associated proteins (RNP fibers) which have resulted from transcription of the DNA in the underlying chromatin segment. In particular, the patterns indicate that the chromatin underlying each array is delimited by specific sites for initiation and termination of transcription. We apply the term transcription unit to a chromatin segment thus bounded. The analysis has further revealed that transcription units can be grouped into two principal classes--ribosomal and nonribosomal. Active transcription units of these two classes differ in DNA content, in their proximity to other active transcription units, and in their chromatin morphology. For certain developmental stages, fiber frequencies (that is, the nubmers of fibers per mum of chromatin) are also useful in distinguishing ribosomal from nonribosomal arrays. The most definitive of the above classification criteria is chromatin morphology as observed under our preparative conditions. We propose that term rho chromatin for the unbeaded or smooth chromatin that underlies nascent ribosomal RNP fibers. DNA in rho chromatin has a calculated packing ratio of approximately 1.2 mum of B structure DNA per mum of chromatin. Nu chromatin is used to designate the beaded chromatin for which we calculate a DNA packing ratio of 1.6-2.3 in our preparations. This calculation for nu chromatin is based on the inference that the beads are nucleosomes (nu bodies, PS particles, unit particles). The beaded morphology is observed between fibers of nonribosomal transcription unit as well as for most fiber-free chromatin. The detection of specific sites of transcriptional initiation and termination and the classification of transcription units can provide a basis for further analysis of transcriptional control.
Animals↗
Electron-microscopic visualization of transcriptionally active and less active chromatin fractions from the rat ventral prostate and their content of histones.
The content of histones in transcriptionally active (euchromatin-like (E)) and transcriptionally less active (heterochromatin-like (H)) fractions from the rat ventral prostate was determined. The absolute amount of total histone was less in the E fraction, which contained relatively more stained histone F2b and F3 and less histone F1 than either the H fraction or unfractionated chromatin. The phosphotungstic-acid-stained E fraction was composed predominantly of shorter (50-500 nm) and thinner (5-15 nm) structures. In some preparations, pieces estimated to be 500-1000 + nm in length were present. Spherical structures, from 10 to 20 nm in diameter, some of which were present as 'dimers,' trimers,' or higher-ordered ensembles were seen in the shadow-case E fraction. The stained or shadow-cast H fraction contained longer (200-2000 + nm) and thicker (congruent to 20 nm) fragments with a more complex substructure. When the shadow-cast H fraction was sufficiently dispersed, it had a nodular or 'beaded' appearance.
Animals↗
RETRACTED: Identification of sumoylation sites in CCDC6, the first identified RET partner gene in papillary thyroid carcinoma, uncovers a mode of regulating CCDC6 function on CREB1 transcriptional activity.
CCDC6 was originally identified in chimeric genes as caused by chromosomal translocation involving the RET protooncogene in some thyroid tumors. Recognised as a 65 kDa pro-apoptotic phosphoprotein, CCDC6 has been enrolled as an ATM substrate that contribute to protect genome integrity by modulating PP4c activity in response to genotoxic stress. Recently, CCDC6 has been identified as a repressor of CREB1-dependent transcription. Sumoylation has emerged as an important mechanism in transcriptional control. Here, we report the identification and characterization of three sites of sumoylation in CCDC6 (K74, K266 and K424) which are highly conserved in vertebrates. We demonstrate that the post-translational modifications by SUMO2 constrain most of the CCDC6 protein in the cytosol and affect its functional interaction with CREB1 with a decrease of CCDC6 repressive function on CREB1 transcriptional activity. Indeed, the impairment of functional outcome of sumoylated CCDC6 is obtained knocking down all three the sumoylation sites. Interestingly, in thyroid cells the SUMO2-mediated CCDC6 post-translational modifications are induced by Forskolin, a cAMP analog. Signal transduction via the cAMP pathway is known to be ubiquitous and represents a major line of communication between many organisms and their environment. We believe that CCDC6 could be an important player in the dynamics of cAMP signaling by fine regulating CREB1 transcriptional activity in normal and transformed thyroid cells.
Animals↗
Isolation of transcriptionally active chromatin from mammalian nucleoli.
Nucleoli isolated from HeLa cells are functionally active but contain large amounts of RNA and proteins (RNA/DNA ratio 1:1; protein/DNA ratio 7:1). We have isolated from the nucleolus a DNA-protein complex that has the characteristics of nucleolar chromatin (RNA/DNA ratio less than 0.05:1; protein/DNA ratio 1.7:1). This nucleolar chromatin has most of the transcriptional activity of the intact nucleolus and, as assayed by circular dichroism and dye binding, has largely preserved its structure. The isolation of a transcriptionally active, fragment of chromatin, which constitutes only a small part of the total genome and codes for only one recognizable product, offers several advantages for the study of chromatin structure and function.
Cell Nucleolus↗
Mega-enhancers compartmentalize transcriptionally active long genes in the brain.
Exceptionally long genes and cis-regulatory enhancers are selectively activated in mammalian brain neurons, and these loci are mutation hotspots in neurological disorders. However, the organization of these large genomic elements at the level of chromosome folding, beyond local enhancer-promoter interactions, remains poorly understood. Here we report the discovery of a genomic subcompartment in the mouse cerebellum formed by near-megabase-long enhancers and their associated long genes encoding synaptic or signalling proteins. Genomic regions within this subcompartment are enriched in the outer half of the nucleus, whereas other transcriptionally active structures are enriched in the nuclear interior. Using an in vivo CRISPR genetic mini screen, we uncover a specific role for the transcription factor Etv1 in coupling the compartmentalization of neuronal long genes with their expression. Together, our study defines mechanisms that organize transcriptionally active genes across chromosomes in the mammalian brain.
Animals↗
Antimony species-dependent enrichment and transcriptional activity of antibiotic and metal resistance genes in the gut microbiome of male mice.
The gut microbiome is a reservoir for antibiotic resistance genes (ARGs) and is sensitive to environmental pollutants. ARGs in environmental and host-associated microbiomes can be enriched by metal(loid)s through co-selection with metal resistance genes (MRGs). However, as a ubiquitous toxic metalloid, antimony (Sb) induced alterations of ARGs in the gut microbiome and the underlying mechanisms remain unclear. Here, by integrating genome-resolved metagenomics and metatranscriptomics, we characterized the genomic potential and transcriptional activity of ARGs and MRGs in the gut microbiome of mice exposed to Sb(III)- and Sb(V)-contaminated drinking water. We found that both Sb(III) and Sb(V) significantly increased ARGs abundance, whereas only Sb(III) enhanced ARGs transcription (288.40 ± 41.67 TPM, P < 0.05). Co-selection of ARGs and MRGs was observed through metagenome-assembled genomes (MAGs) analysis, and key taxa driving this process were identified (e.g., Eubacterium_J and Lachnospiraceae_COE1). Sb(III), but not Sb(V), induced co-regulation of macrolide-lincosamide-streptogramin resistance genes and arsRABC operon. A potentially higher risk of ARG dissemination under Sb(III) stress was suggested by the increased abundance and transcription of mobile genetic elements (MGEs). This study advances our understanding of the interactions between Sb and ARGs in the gut microbiome and highlights the potential chemical species-dependent enrichment and transcriptional activation of ARGs.
Antibiotic resistance gene↗
The farnesoid X receptor activates transcription independently of RXR at non-canonical response elements.
The farnesoid X receptor (FXR) is a nuclear receptor (NR) known to obligately heterodimerize with the retinoid X receptor (RXR). FXR is expressed as four isoforms (α1-α4) that drive transcription from IR-1 (inverted repeat-1) response elements (REs). Recently, we found that FXR isoforms α2/α4 also activate transcription from non-canonical ER-2 (everted repeat-2) REs, mediating most metabolic effects of general FXR activation. Here, we explored molecular determinants of regulation by FXRα2 from ER-2 REs through quantitative interaction proteomics, site-directed mutagenesis and transcriptomics. We discovered FXRα2 binds to and activates ER-2 elements in vitro and in reporter assays independently of RXR. Genome-wide binding analysis in mouse liver revealed higher ER-2 motif enrichment in FXR sites lacking RXR. Abrogation of FXRα2:RXR heterodimerization abolished IR-1, but preserved ER-2 transactivation. Transcriptome-wide, RXR overexpression inhibited 25% of FXRα2 targets in HepG2. These genes were specifically activated by the heterodimerization-deficient mutant FXRα2L434R, enriched for ER-2 motifs at their promoters, and involved in lipid metabolism and ammonia detoxification. In conclusion, RXR acts as a molecular switch, inhibiting FXRα2 activation from ER-2 while enhancing it from canonical IR-1 REs. Our results showcase FXR as the first NR with isoform-specific RXR-independent REs, highlighting a new layer of regulation and complexity for RXR-heterodimerizing NRs.
Humans↗