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Abscisic acid (ABA) reduces accumulation of potentially toxic cadmium (Cd) in plants. How the ABA signal is transmitted to modulate Cd uptake remains largely unclear. Here, we report that the basic region/Leu zipper transcription factor ABSCISIC ACID-INSENSITIVE5 (ABI5), a central ABA signaling molecule, is involved in ABA-repressed Cd accumulation in plants by physically interacting with a previously uncharacterized R2R3-type MYB transcription factor, MYB49. Overexpression of the Cd-induced MYB49 gene in Arabidopsis (Arabidopsis thaliana) resulted in a significant increase in Cd accumulation, whereas myb49 knockout plants and plants expressing chimeric repressors of MYB49:ERF-associated amphiphilic repression motif repression domain (SRDX49) exhibited reduced accumulation of Cd. Further investigations revealed that MYB49 positively regulates the expression of the basic helix-loop-helix transcription factors bHLH38 and bHLH101 by directly binding to their promoters, leading to activation of IRON-REGULATED TRANSPORTER1, which encodes a metal transporter involved in Cd uptake. MYB49 also binds to the promoter regions of the heavy metal-associated isoprenylated plant proteins (HIPP22) and HIPP44, resulting in up-regulation of their expression and subsequent Cd accumulation. On the other hand, as a feedback mechanism to control Cd uptake and accumulation in plant cells, Cd-induced ABA up-regulates the expression of ABI5, whose protein product interacts with MYB49 and prevents its binding to the promoters of downstream genes, thereby reducing Cd accumulation. Our results provide new insights into the molecular feedback mechanisms underlying ABA signaling-controlled Cd uptake and accumulation in plants.

Key messageThis paper demonstrates that BBX28 and BBX29 proteins in Arabidopsis promote flowering in association with the CO-FT regulatory module at low ambient temperature under LD conditions.Flowering plants integrate internal developmental signals with external environmental stimuli for precise flowering time control. The expression of BBX29 is up-regulated by low temperature treatment, but the biological function of BBX29 in low temperature response is unknown. In the current study, we examined the biological role of BBX29 and its close-related protein BBX28 in flowering time control under long-day conditions. Although neither BBX28 single mutant nor BBX29 single mutant has a flowering-associated phenotype, the bbx28 bbx29 double mutant plants have an obvious delayed flowering phenotype grown at low ambient temperature (16°C) compared to the wild-type (WT) plants. The expression of FT and TSF was lower in bbx28 bbx29 double mutant plants than in wild-type plants at 16°C. Both BBX28 and BBX29 interact with CONSTANS (CO), an important flowering integrator that directly binds to the FLOWERING LOCUS T (FT) promoter. In the effector-reporter assays, transcriptional activation activity of CO on the FT promoter was reduced in bbx28 bbx29 double mutant plants compared to that in WT plants. Taken together, our results reveal that BBX28 and BBX29 are promoters of flowering in Arabidopsis, especially at low ambient temperature.

Key Points Gene transcription is the first step in the expression of the genome. The regulation of transcription underlies organism development and cell differentiation. Transcription of eukaryotic protein-coding genes commences with the assembly of a conserved initiation complex, consisting of RNA polymerase II (Pol II) and the general transcription factors, at promoter DNA. Understanding how transcription initiates requires knowledge of the 3D structure of the Pol II initiation complex and intermediates on the initiation pathway. After two decades of research, the structural basis of transcription initiation is emerging. Many crystal structures of components of the initiation complex have been resolved, and structural information on Pol II complexes with general transcription factors has been obtained recently. Available structural data outline how Pol II cooperates with the general transcription factors to bind to and open promoter DNA and to direct RNA synthesis and escape from promoters. In the future, the structures of other initiation factors, which are not yet known, should be determined and the dynamics of the transition from transcription initiation to elongation should be analysed. Transcription of eukaryotic protein-coding genes requires the assembly of a conserved initiation complex at promoter DNA. Structural information on this complex, which comprises RNA polymerase II and the general transcription factors, is beginning to reveal the mechanisms underlying the initial steps of transcription, such as the recognition and opening of promoter DNA. Transcription of eukaryotic protein-coding genes commences with the assembly of a conserved initiation complex, which consists of RNA polymerase II (Pol II) and the general transcription factors, at promoter DNA. After two decades of research, the structural basis of transcription initiation is emerging. Crystal structures of many components of the initiation complex have been resolved, and structural information on Pol II complexes with general transcription factors has recently been obtained. Although mechanistic details await elucidation, available data outline how Pol II cooperates with the general transcription factors to bind to and open promoter DNA, and how Pol II directs RNA synthesis and escapes from the promoter.

Structural models of psychopathology consistently identify internalizing (INT) and externalizing (EXT) specific factors as well as a superordinate factor that captures their shared variance, the factor. Questions remain, however, about the meaning of these data-driven dimensions and the interpretability and distinguishability of the larger nomological networks in which they are embedded. The sample consisted of 10 645 youth aged 9-10 years participating in the multisite Adolescent Brain and Cognitive Development (ABCD) Study. , INT, and EXT were modeled using the parent-rated Child Behavior Checklist (CBCL). Patterns of associations were examined with variables drawn from diverse domains including demographics, psychopathology, temperament, family history of substance use and psychopathology, school and family environment, and cognitive ability, using instruments based on youth-, parent-, and teacher-report, and behavioral task performance. exhibited a broad pattern of statistically significant associations with risk variables across all domains assessed, including temperament, neurocognition, and social adversity. The specific factors exhibited more domain-specific patterns of associations, with INT exhibiting greater fear/distress and EXT exhibiting greater impulsivity. In this largest study of hierarchical models of psychopathology to date, we found that , INT, and EXT exhibit well-differentiated nomological networks that are interpretable in terms of neurocognition, impulsivity, fear/distress, and social adversity. These networks were, in contrast, obscured when relying on the a priori Internalizing and Externalizing dimensions of the CBCL scales. Our findings add to the evidence for the validity of , INT, and EXT as theoretically and empirically meaningful broad psychopathology liabilities.

DNA binding-with-one-finger (Dof) proteins are plant-specific transcription factors closely associated with a variety of physiological processes. Here, we show that the Dof protein family in Arabidopsis (Arabidopsis thaliana) functions in leaf senescence. Disruption of Dof2.1, a jasmonate (JA)-inducible gene, led to a marked reduction in promotion of leaf senescence and inhibition of root development as well as dark-induced and age-dependent leaf senescence, while overexpression of Dof2.1 promoted these processes. Additionally, the dof2.1 knockout mutant showed almost no change in the transcriptome in the absence of JA; in the presence of JA, expression of many senescence-associated genes, including MYC2, which encodes a central regulator of JA responses, was induced to a lesser extent in the dof2.1 mutant than in the wild type. Furthermore, direct activation of the MYC2 promoter by Dof2.1, along with the results of epistasis analysis, indicated that Dof2.1 enhances leaf senescence mainly by promoting MYC2 expression. Interestingly, MYC2 was also identified as a transcriptional activator responsible for JA-inducible expression of Dof2.1. Based on these results, we propose that Dof2.1 acts as an enhancer of JA-induced leaf senescence through the MYC2–Dof2.1–MYC2 feedforward transcriptional loop.

Despite statistical evidence of a general factor of psychopathology (i.e., -factor), there is little agreement about what the -factor represents. Researchers have proposed five theories: dispositional negative emotionality (neuroticism), impulsive responsivity to emotions (impulsivity), thought dysfunction, low cognitive functioning, and impairment. These theories have primarily been inferred from patterns of loadings of diagnoses on -factors with different sets of diagnoses included in different studies. Researchers who have directly examined these theories of have examined a subset of the theories in any single sample, limiting the ability to compare the size of their associations with a -factor. In a sample of adults ( = 1833, = 34.20, 54.4% female, 53.3% white) who completed diagnostic assessments, self-report measures, and cognitive tests, we evaluated statistical -factor structures across modeling approaches and compared the strength of associations among the -factor and indicators of each of these five theories. We found consistent evidence of the -factor's unidimensionality across one-factor and bifactor models. The -factor was most strongly and similarly associated with neuroticism ( = .88), impairment ( = .88), and impulsivity ( = .87), χ (1)s < .15, s > .70, and less strongly associated with thought dysfunction ( = .78), χ (1)s > 3.92, s < .05, and cognitive functioning ( = -.25), χ (1)s > 189.56, s < .01. We discuss a tripartite definition of that involves the transaction of impulsive responses to frequent negative emotions leading to impairment that extends and synthesizes previous theories of psychopathology.

The regulated transcription of genes determines cell identity and function. Recent structural studies have elucidated mechanisms that govern the regulation of transcription by RNA polymerases during the initiation and elongation phases. Microscopy studies have revealed that transcription involves the condensation of factors in the cell nucleus. A model is emerging for the transcription of protein-coding genes in which distinct transient condensates form at gene promoters and in gene bodies to concentrate the factors required for transcription initiation and elongation, respectively. The transcribing enzyme RNA polymerase II may shuttle between these condensates in a phosphorylation-dependent manner. Molecular principles are being defined that rationalize transcriptional organization and regulation, and that will guide future investigations. Structural and microscopy studies of gene transcription underpin a model in which phosphorylation controls the shuttling of RNA polymerase II between promoter and gene-body condensates to regulate transcription initiation and elongation.

Transcription and regulation of genes originate from transcription pre-initiation complexes (PICs). Their structural and positional organization across eukaryotic genomes is unknown. Here we applied lambda exonuclease to chromatin immunoprecipitates (termed ChIP-exo) to examine the precise location of 6,045 PICs in Saccharomyces . PICs, including RNA polymerase II and protein complexes TFIIA, TFIIB, TFIID (or TBP), TFIIE, TFIIF, TFIIH and TFIIK were positioned within promoters and excluded from coding regions. Exonuclease patterns were in agreement with crystallographic models of the PIC, and were sufficiently precise to identify TATA-like elements at so-called TATA-less promoters. These PICs and their transcription start sites were positionally constrained at TFIID-engaged downstream +1 nucleosomes. At TATA-box-containing promoters, which are depleted of TFIID, a +1 nucleosome was positioned to be in competition with the PIC, which may allow greater latitude in start-site selection. Our genomic localization of messenger RNA and non-coding RNA PICs reveals that two PICs, in inverted orientation, may occupy the flanking borders of nucleosome-free regions. Their unambiguous detection may help distinguish bona fide genes from transcriptional noise. Ultra-high-resolution mapping of the eukaryotic transcription machinery across the yeast genome reveals several unifying principles of pre-initiation complexes at coding and non-coding genes. Mapping eukaryotic pre-initiation complexes Assembly of the RNA polymerase II pre-initiation complex (PIC) is a crucial early step in gene transcription. Here, a high-resolution technique termed ChIP-exo is used to map precisely the binding and composition of PICs across the yeast genome. The findings include the presence of two divergently oriented PICs at promoters, and a broader role for TATA-like elements than was previously appreciated. This allows new insights into the mechanism of transcription.

It has long been assumed that lifespan and healthspan correlate strongly, yet the two can be clearly dissociated 1 – 6 . Although there has been a global increase in human life expectancy, increasing longevity is rarely accompanied by an extended healthspan 4 , 7 . Thus, understanding the origin of healthy behaviours in old people remains an important and challenging task. Here we report a conserved epigenetic mechanism underlying healthy ageing. Through genome-wide RNA-interference-based screening of genes that regulate behavioural deterioration in ageing Caenorhabditis elegans , we identify 59 genes as potential modulators of the rate of age-related behavioural deterioration. Among these modulators, we found that a neuronal epigenetic reader, BAZ-2, and a neuronal histone 3 lysine 9 methyltransferase, SET-6, accelerate behavioural deterioration in C. elegans by reducing mitochondrial function, repressing the expression of nuclear-encoded mitochondrial proteins. This mechanism is conserved in cultured mouse neurons and human cells. Examination of human databases 8 , 9 shows that expression of the human orthologues of these C. elegans regulators, BAZ2B and EHMT1, in the frontal cortex increases with age and correlates positively with the progression of Alzheimer’s disease. Furthermore, ablation of Baz2b, the mouse orthologue of BAZ-2, attenuates age-dependent body-weight gain and prevents cognitive decline in ageing mice. Thus our genome-wide RNA-interference screen in C. elegans has unravelled conserved epigenetic negative regulators of ageing, suggesting possible ways to achieve healthy ageing. Two epigenetic regulators—identified in an RNA interference screen in Caenhorhabditis elegans , and conserved in mammals—diminish mitochondrial function and accelerate the age-related deterioration of behaviour.

Viroids, a fascinating group of plant pathogens, are subviral agents composed of single-stranded circular noncoding RNAs. It is well-known that nuclear-replicating viroids exploit host DNA-dependent RNA polymerase II (Pol II) activity for transcription from circular RNA genome to minus-strand intermediates, a classic example illustrating the intrinsic RNA-dependent RNA polymerase activity of Pol II. The mechanism for Pol II to accept single-stranded RNAs as templates remains poorly understood. Here, we reconstituted a robust in vitro transcription system and demonstrated that Pol II also accepts minus-strand viroid RNA template to generate plus-strand RNAs. Further, we purified the Pol II complex on RNA templates for nano-liquid chromatography-tandem mass spectrometry analysis and identified a remodeled Pol II missing Rpb4, Rpb5, Rpb6, Rpb7, and Rpb9, contrasting to the canonical 12-subunit Pol II or the 10-subunit Pol II core on DNA templates. Interestingly, the absence of Rpb9, which is responsible for Pol II fidelity, explains the higher mutation rate of viroids in comparison to cellular transcripts. This remodeled Pol II is active for transcription with the aid of TFIIIA-7ZF and appears not to require other canonical general transcription factors (such as TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH, and TFIIS), suggesting a distinct mechanism/machinery for viroid RNA-templated transcription. Transcription elongation factors, such as FACT complex, PAF1 complex, and SPT6, were also absent in the reconstituted transcription complex. Further analyses of the critical zinc finger domains in TFIIIA-7ZF revealed the first three zinc finger domains pivotal for RNA template binding. Collectively, our data illustrated a distinct organization of Pol II complex on viroid RNA templates, providing new insights into viroid replication, the evolution of transcription machinery, as well as the mechanism of RNA-templated transcription.