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In E. coli , the genes of the D-xylonate catabolic pathway are present in two distinct operons, yagEFG  and yjhIHG , which are part of two cryptic phages found in the genome of this bacterium. These operons are under the control of two transcription factors: XynR which acts as a repressor of yagEFG and yjhI which is an activator of yjhIHG . Although D-xylonate is known to induce these two operons, the true inducer has not been identified yet. Through the construction of biosensors based on xynR and yjhI , using syfp2 as reporter gene in combination with mutants of genes involved in D-xylonate catabolism, it has been demonstrated that the effector of these operons is 2-keto-3-deoxy-D-xylonate, which is formed by the dehydration of D-xylonate catalyzed by the dehydratases encoded by yagF and yjhG genes. Building on the finding that these two operons were also upregulated in E. coli challenged with high concentration of platform molecule 2,4-dihydroxybutyric acid, it is reported that both XynR- and YjhI-based biosensors were also responsive to the intermediate non-natural molecule 2-oxo-4-hydroxybutyric acid, with characteristic performances in terms of response threshold, sensitivity, cooperativity, and dynamic response comparable to those of the natural effector. Given that the bottlenecks in the production of 2,4-dihydroxybutyrate from C2 and C5/C6 carbon are D-threonate dehydratase and L-homoserine transaminase, respectively, which catalyze the formation of 2-oxo-4-hydroxybutyric acid from either D-threonate or homoserine, we showed that XynR and YjhI-based biosensors could be efficient tools for the screening and selection of more active enzymes producing this compound, thereby improving the production of 2,4-dihydroxybutyrate.

Plants must effectively defend against biotic and abiotic stresses to survive in nature. However, this defense is costly and is often accompanied by significant growth inhibition. How plants coordinate the fluctuating growth-defense dynamics is not well understood and remains a fundamental question. Jasmonate (JA) and gibberellic acid (GA) are important plant hormones that mediate defense and growth, respectively. Binding of bioactive JA or GA ligands to cognate receptors leads to proteasome-dependent degradation of specific transcriptional repressors (the JAZ or DELLA family of proteins), which, at the resting state, represses cognate transcription factors involved in defense (e.g., MYCs) or growth [e.g. phytochrome interacting factors (PIFs)]. In this study, we found that the coi1 JA receptor mutants of rice (a domesticated monocot crop) and Arabidopsis (a model dicot plant) both exhibit hallmark phenotypes of GA-hypersensitive mutants. JA delays GA-mediated DELLA protein degradation, and the della mutant is less sensitive to JA for growth inhibition. Overexpression of a selected group of JAZ repressors in Arabidopsis plants partially phenocopies GA-associated phenotypes of the coi1 mutant, and JAZ9 inhibits RGA (a DELLA protein) interaction with transcription factor PIF3. Importantly, the pif quadruple (pifq) mutant no longer responds to JA-induced growth inhibition, and overexpression of PIF3 could partially overcome JA-induced growth inhibition. Thus, a molecular cascade involving the COI1–JAZ–DELLA–PIF signaling module, by which angiosperm plants prioritize JA-mediated defense over growth, has been elucidated.

Jasmonates (JAs) mediate plant responses to insect attack, wounding, pathogen infection, stress, and UV damage and regulate plant fertility, anthocyanin accumulation, trichome formation, and many other plant developmental processes. Arabidopsis thaliana Jasmonate ZIM-domain (JAZ) proteins, substrates of the CORONATINE INSENSITIVE1 (COl1)-based SCF COl ¹ complex, negatively regulate these plant responses. Little is known about the molecular mechanism for JA regulation of anthocyanin accumulation and trichome initiation. In this study, we revealed that JAZ proteins interact with bHLH (Transparent Testa8, Glabra3 [GL3], and Enhancer of Glabra3 [EGL3]) and R2R3 MYB transcription factors (MYB75 and Glabra1), essential components of WD-repeat/bHLH/MYB transcriptional complexes, to repress JA-regulated anthocyanin accumulation and trichome initiation. Genetic and physiological evidence showed that JA regulates WD-repeat/bHLH/MYB complex-mediated anthocyanin accumulation and trichome initiation in a COl1-dependent manner. Overexpression of the MYB transcription factor MYB75 and bHLH factors (GL3 and EGL3) restored anthocyanin accumulation and trichome initiation in the col1 mutant, respectively. We speculate that the JA-induced degradation of JAZ proteins abolishes the interactions of JAZ proteins with bHLH and MYB factors, allowing the transcriptional function of WD-repeat/bHLH/MYB complexes, which subsequently activate respective downstream signal cascades to modulate anthocyanin accumulation and trichome initiation.

An interlocking transcriptional-translational feedback loop of clock-associated genes is thought to be the central oscillator of the circadian clock in plants. TIMING OF CAB EXPRESSION1 (also called PSEUDO-RESPONSE REGULATOR1 [PRR1]) and two MYB transcription factors, CIRCADIAN CLOCK ASSOCIATED1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY), play pivotal roles in the loop. Genetic studies have suggested that PRR9, PRR7, and PRR5 also act within or close to the loop; however, their molecular functions remain unknown. Here, we demonstrate that PRR9, PRR7, and PRR5 act as transcriptional repressors of CCA1 and LHY. PRR9, PRR7, and PRR5 each suppress CCA1 and LHY promoter activities and confer transcriptional repressor activity to a heterologous DNA binding protein in a transient reporter assay. Using a glucocorticoid-induced PRR5-GR (glucorticoid receptor) construct, we found that PRR5 directly downregulates CCA1 and LHY expression. Furthermore, PRR9, PRR7, and PRR5 associate with the CCA1 and LHY promoters in vivo, coincident with the timing of decreased CCA1 and LHY expression. These results suggest that the repressor activities of PRR9, PRR7, and PRR5 on the CCA1 and LHY promoter regions constitute the molecular mechanism that accounts for the role of these proteins in the feedback loop of the circadian clock.

Various pregnancy complications, such as severe forms of preeclampsia or intrauterine growth restriction, are thought to arise from failures in the differentiation of human placental trophoblasts. Progenitors of the latter either develop into invasive extravillous trophoblasts, remodeling the uterine vasculature, or fuse into multinuclear syncytiotrophoblasts transporting oxygen and nutrients to the growing fetus. However, key regulatory factors controlling trophoblast self-renewal and differentiation have been poorly elucidated. Using primary cells, three-dimensional organoids, and CRISPR-Cas9 genome-edited JEG-3 clones, we herein show that YAP, the transcriptional coactivator of the Hippo signaling pathway, promotes maintenance of cytotrophoblast progenitors by different genomic mechanisms. Genetic or chemical manipulation of YAP in these cellular models revealed that it stimulates proliferation and expression of cell cycle regulators and stemness-associated genes, but inhibits cell fusion and production of syncytiotrophoblast (STB)-specific proteins, such as hCG and GDF15. Genome-wide comparisons of primary villous cytotrophoblasts overexpressing constitutively active YAP-5SA with YAP KO cells and syncytializing trophoblasts revealed common target genes involved in trophoblast stemness and differentiation. ChIP-qPCR unraveled that YAP-5SA overexpression increased binding of YAP–TEAD4 complexes to promoters of proliferation-associated genes such as CCNA and CDK6. Moreover, repressive YAP–TEAD4 complexes containing the histone methyltransferase EZH2 were detected in the genomic regions of the STB-specific CGB5 and CGB7 genes. In summary, YAP plays a pivotal role in the maintenance of the human placental trophoblast epithelium. Besides activating stemness factors, it also directly represses genes promoting trophoblast cell fusion.

Cytokinin fulfills its diverse roles in planta through a series of transcriptional responses. We identify the in vivo DNA binding site profiles for three genetically redundant type-B ARABIDOPSIS RESPONSE REGULATORS (B-ARRs): ARR1, ARR10, and ARR12. The expression and genome-wide DNA binding locations of the three B-ARRs extensively overlap. Constructing a primary cytokinin response transcriptional network reveals a recurring theme of widespread cross-regulation between the components of the cytokinin pathway and other plant hormone pathways. The B-ARRs are found to have similar DNA binding motifs, though sequences flanking the core motif were degenerate. Cytokinin treatments amalgamate the three different B-ARRs motifs to identical DNA binding signatures (AGATHY, H(a/t/c), Y(t/c)) which suggests cytokinin may regulate binding activity of B-ARR family members. Furthermore, we find that WUSCHEL , a key gene required for apical meristem maintenance, is a cytokinin-dependent B-ARR target gene, demonstrating the importance of the cytokinin transcription factor network in shoot development. Cytokinin regulates gene expression by activation of ARR transcription factors. Here, the authors use ChIP-seq to show how three type B-ARRs mediate cytokinin response in Arabidopsis and provide evidence that cytokinin regulates meristem development by promoting B-ARR binding to WUSCHEL .

Light and temperature are two important environmental signals to plants. After dawn, photo-activated phytochromes translocate into the nucleus and interact with a family of negative basic helix-loop-helix PIF regulators. Subsequent phosphorylation and degradation of PIFs triggers a series of photomorphogenic responses. However, excess light can damage the photosynthetic apparatus and leads to photoinhibition. Plants acclimate to a balanced state of photomorphogenesis to avoid photodamage. Here, we show that upregulation of PIF4 expression by SHB1 and CCA1 under red light represents a desensitization step. After dawn, the highly expressed circadian clock protein CCA1 brings circadian signals to the regulatory region of the PIF4 signaling hub. Recruitment of SHB1 by CCA1 modulates red light-specific induction of PIF4 expression thus integrating circadian and light signals. As noon approaches and light intensity and ambient temperature tend to increase, the SHB1–CCA1 interaction sustains PIF4 expression to trigger thermomorphogenic responses to changing light and temperature conditions. The PIF4 transcription factor promotes adaptation to elevated temperature but is degraded under red light to trigger photomorphogenesis. Here Sun et al . show that the core circadian component CCA1 recruits SHB1 to sustain PIF4 expression after dawn to balance thermomorphogenesis and light responses.

• Proper regulation of seed germination is essential for the successful propagation of a plant. The transcription factor ABSCISIC ACID INSENSITIVE5 (ABI5) of the abscisic acid (ABA) signaling pathway plays a central role in the inhibition of seed germination. ABI5 is precisely regulated by the core ABA signaling components and multiple other factors. However, the complex regulatory network of ABI5 remains largely unknown. • In this study, we determined the biochemical interaction between ABI5 and the BRINSENSITIVE1 (BRI1)-EMS-SUPPRESSOR1 (BES1) transcription factor of the brassinosteroid (BR) signaling pathway, as well as the function of BES1 regulating ABI5 during seed germination in Arabidopsis. • BES1 directly interacts with ABI5 both in vitro and in vivo. The bZIP domain of ABI5, which is responsible for DNA binding, is critical for ABI5 binding to BES1. The interaction of BES1 with ABI5 significantly suppressed the binding of ABI5 to the promoter regions of downstream genes, which resulted in their reduced expression and consequently facilitated seed germination. • This study shed new light on the coordination of multiple signaling pathways during seed germination. In particular, BES1 directly binds to ABI5, which interferes with its transcriptional activity and suppresses ABA signaling output.

PRDM (PRDI-BF1 and RIZ homology domain containing) family members are sequence-specific transcriptional regulators involved in cell identity and fate determination, often dysregulated in cancer. The PRDM15 gene is of particular interest, given its low expression in adult tissues and its overexpression in B-cell lymphomas. Despite its well characterized role in stem cell biology and during early development, the role of PRDM15 in cancer remains obscure. Herein, we demonstrate that while PRDM15 is largely dispensable for mouse adult somatic cell homeostasis in vivo, it plays a critical role in B-cell lymphomagenesis. Mechanistically, PRDM15 regulates a transcriptional program that sustains the activity of the PI3K/AKT/mTOR pathway and glycolysis in B-cell lymphomas. Abrogation of PRDM15 induces a metabolic crisis and selective death of lymphoma cells. Collectively, our data demonstrate that PRDM15 fuels the metabolic requirement of B-cell lymphomas and validate it as an attractive and previously unrecognized target in oncology. The transcriptional regulator PRDM15 is expressed at low levels in normal tissues but overexpressed in B-cell lymphomas. Here, the authors show that PRDM15 depletion does not affect adult somatic cell homeostasis but leads to a metabolic crisis which impairs B-cell lymphomagenesis.

Plant cells are totipotent and competent to regenerate from differentiated organs. It has been known for six decades that cytokinin-rich medium induces shoot regeneration from callus cells. However, the underlying molecular mechanism remains elusive. The homeodomain transcription factor WUSCHEL (WUS) is essential for de novo establishment of the shoot stem cell niche in We found that WUS-positive (WUS ) cells mark the shoot progenitor region during regeneration. A cytokinin-rich environment initially promotes the removal of the repressive histone mark H3K27me3 at the locus in a cell cycle-dependent manner. Subsequently, the B-type ARABIDOPSIS RESPONSE REGULATORs (ARRs) ARR1, ARR2, ARR10, and ARR12, which function as transcriptional activators in the cytokinin signaling pathway, spatially activate expression through binding with microRNA165/6-targeted HD-ZIP III transcription factors. Thus, our results provide important insights into the molecular framework for cytokinin-directed shoot regeneration and reveal a two-step mechanism for de novo activation of .