We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) 1-3 of esophageal squamous cell carcinoma (ESCC) in ethnic Chinese (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study, and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% CI 0.82-0.88; P=7.72x10−20) and rs1642764 at 17p13.1 (per-allele OR= 0.88, 95% CI 0.85-0.91; P=3.10x10−13). rs7447927 is a synonymous single nucleotide polymorphism (SNP) in TMEM173 and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR=1.33, 95% CI 1.22-1.46; P=1.99x10−10). Our joint analysis identified new ESCC susceptibility loci overall as well as a new locus unique to the ESCC high risk Taihang Mountain region.
The plant hormone gibberellin plays key roles in almost all aspects of plant development, but its detailed function and underlying regulatory mechanism in embryo development are not yet clearly defined. Here, we illustrate an essential role of gibberellin in late embryogenesis of Arabidopsis. Bioactive gibberellins are highly biosynthesized during the late developmental stage of embryos. At that time, deficiency in gibberellin biosynthesis or signalling results in an abnormal embryo phenotype characterized by less-developed cotyledons and shortened embryo axis. In contrast, gibberellin overdose leads to a significantly larger size of mature embryo. We reveal that the gibberellin signalling repressor DELLA interact with LEAFY COTYLEDON1 (LEC1), the key regulator in late embryogenesis. Gibberellin triggers the degradation of DELLAs to relieve their repression of LEC1, thus promoting auxin accumulation to facilitate embryo development. Therefore, we uncover a space/time-specific role of gibberellin in regulating late embryogenesis through the gibberellin-DELLA-LEC1 signalling cascade, providing a novel mechanistic understanding of how phytohormones regulate embryogenesis.
To facilitate the pseudochromosomes assembly and gene cloning in rapeseed, we developed a reference genetic population/map (named BnaZNF2) from two sequenced cultivars, Zhongshuang11 and No.73290, those exhibit significant differences in many traits, particularly yield components. The BnaZNF2 genetic map exhibited perfect collinearity with the physical map of B. napus, indicating its high quality. Comparative mapping revealed several genomic rearrangements between B. napus and B. rapa or B. oleracea. A total of eight and 16 QTLs were identified for pod number and seed number per pod, respectively, and of which three and five QTLs are identical to previously identified ones, whereas the other five and 11 are novel. Two new major QTL respectively for pod number and seed number per pod, qPN.A06-1 and qSN.A06-1 (R2 = 22.8% and 32.1%), were colocalised with opposite effects, and only qPN.A06-1 was confirmed and narrowed by regional association analysis to 180 kb including only 33 annotated genes. Conditional QTL analysis and subsequent NILs test indicated that tight linkage, rather than pleiotropy, was the genetic causation of their colocalisation. Our study demonstrates potential of this reference genetic population/map for precise QTL mapping and as a base for positional gene cloning in rapeseed.
Seed number per pod (SNPP) is one of the major yield components and breeding targets in rapeseed that shows great variation and is invaluable for genetic improvement. To elucidate the genetic architecture and uncover the mechanism of SNPP, we identified five quantitative trait loci (QTLs) using the BnaZNRIL population, which were integrated with those of previous studies by physical map to demonstrate a complex and relatively complete genetic architecture of SNPP. A major QTL, qSN.A6, was successfully fine-mapped from 1910 to 267 kb using near-isogenic line (NIL). In addition, qSN.A6 exhibited an antagonistic pleiotropy on seed weight (SW), which is caused by a physiological interaction in which SNPP acts “upstream” of SW. Because the negative effect of qSN.A6 on SW cannot fully counteract its positive effect on SNPP, it also enhanced the final yield (17.4%), indicating its great potential for utilization in breeding. The following genetic and cytological experiments further confirmed that the different rate of ovule abortion was responsible for the ~5 seed difference between Zhongshuang11 and NIL-qSN.A6. This systematic approach to dissecting the comprehensive genetic architecture of SNPP and characterizing the underlying mechanism has advanced the understanding of SNPP and will facilitate the development of high-yield cultivars.
Plants maintain a dynamic balance between growth and defense , and optimize allocation of resources for survival under constant pathogen infections. However, the underlying molecular regulatory mechanisms, especially in response to biotrophic bacterial infection, remain elusive. Here, we demonstrate that DELLA proteins and EDS1, an essential resistance regulator, form a central module modulating plant growth-defense tradeoffs via direct interaction. When infected by Pst DC3000, EDS1 rapidly promotes salicylic acid (SA) biosynthesis and resistance-related gene expression to prime defense response, while pathogen infection stabilizes DELLA proteins RGA and RGL3 to restrict growth in a partially EDS1-dependent manner, which facilitates plants to develop resistance to pathogens. However, the increasingly accumulated DELLAs interact with EDS1 to suppress SA overproduction and excessive resistance response. Taken together, our findings reveal a DELLA-EDS1-mediated feedback regulatory loop by which plants maintain the subtle balance between growth and defense to avoid excessive growth or defense in response to constant biotrophic pathogen attack.
The flowering time of higher plants is controlled by environmental cues and intrinsic signals. In Arabidopsis (), flowering is accelerated by exposure to long-day conditions via the key photoperiod-induced factor FLOWERING LOCUS T (FT). Nuclear Factor-Y subunit C (NF-YC) proteins function as important mediators of epigenetic marks in different plant developmental stages and play an important role in the regulation of transcription, but the mechanistic details of this remain unknown. In this study, we show that Arabidopsis NF-YC homologs temporally interact with the histone methyltransferase CURLY LEAF (CLF) during the flowering transition. The binding of NF-YC antagonizes the association of CLF with chromatin and the CLF-dependent deposition of H3 lysine-27 trimethylation, thus relieving the repression of transcription and facilitating flowering under long-day conditions. Our findings reveal a novel mechanism of NF-YC/CLF-mediated epigenetic regulation of activation in photoperiod-induced flowering and, consequently, contribute to our understanding of how plants control developmental events in a temporal-specific regulatory manner.
Light functions as the primary environmental stimulus and brassinosteroids (BRs) as important endogenous growth regulators throughout the plant lifecycle. Photomorphogenesis involves a series of vital developmental processes that require the suppression of BR-mediated seedling growth, but the mechanism underlying the light-controlled regulation of the BR pathway remain unclear. Here, we reveal that nuclear factor YC proteins (NF-YCs) function as essential repressors of the BR pathway during light-controlled hypocotyl growth in Arabidopsis thaliana. In the light, NF-YCs inhibit BR biosynthesis by directly targeting the promoter of the BR biosynthesis gene BR6ox2 and repressing its transcription. NF-YCs also interact with BIN2, a critical repressor of BR signaling, and facilitate its stabilization by promoting its Tyr200 autophosphorylation, thus inhibiting the BR signaling pathway. Consistently, loss-of-function mutants of NF-YCs show etiolated growth and constitutive BR responses, even in the light. Our findings uncover a dual role of NF-YCs in repressing BR biosynthesis and signaling, providing mechanistic insights into how light antagonizes the BR pathway to ensure photomorphogenic growth in Arabidopsis.
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