Biology subjects

Liang, G.

Publications and source records attributed to Liang, G..

At least 37 records · Page 2Linked to original sources

bioRxiv2023

Transcriptional profiling of skin cancer NK cells reveals the elevated glucocorticoid signaling switches their anti-tumor characteristics to a homeostatic feature

Natural killer (NK) cells are potent mediators of anti-tumor immunity, yet their functions are frequently subverted by tumor microenvironment-driven immunosuppression. Here, we dissect the molecular mechanisms underlying NK cell dysfunction in cutaneous malignancies and identify a paradoxical cytokine shift in tumor-associated NK cells-reduced production of IFN-{gamma} and TNF- alongside elevated amphiregulin (AREG), an EGFR ligand linked to tumor progression. Single-cell transcriptomic analysis indicates that this reprogramming correlates with elevated glucocorticoid receptor (GR/NR3C1) pathway activity in tumor-infiltrating NK cells. Functional validation demonstrated that glucocorticoids specifically induce AREG production in NK cells, with tumor-associated prostaglandin E2 (PGE2) augmenting this response. Genetic ablation or pharmacological inhibition of NR3C1 abolished glucocorticoid-driven AREG induction. Moreover, primary GR activation established persistent chromatin accessibility at the AREG locus, sensitizing NK cells to enhanced AREG production upon secondary glucocorticoid exposure. Functionally, AREG counteracts NK cell-mediated tumor apoptosis, while adoptive transfer of AREG-deficient human NK cells significantly suppressed melanoma, cutaneous squamous cell carcinoma (cSCC), and hepatocellular carcinoma growth in NCG mice. These findings establish the GR-AREG axis as a multi-layered therapeutic target for restoring NK cell anti-tumor function. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/557530v3_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@1ef982forg.highwire.dtl.DTLVardef@f036a7org.highwire.dtl.DTLVardef@941abborg.highwire.dtl.DTLVardef@1670d23_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2023

Inhibiting Stromal Class I HDACs Curbs Pancreatic Cancer Progression

Oncogenic lesions in pancreatic ductal adenocarcinoma (PDAC) hijack the epigenetic machinery in stromal components to establish a desmoplastic and therapeutic resistant tumor microenvironment (TME). Here we identify Class I histone deacetylases (HDACs) as key epigenetic factors facilitating the induction of pro-desmoplastic and pro-tumorigenic transcriptional programs in pancreatic stromal fibroblasts. Mechanistically, HDAC-mediated changes in chromatin architecture enable the activation of pro-desmoplastic programs directed by serum response factor (SRF) and forkhead box M1 (FOXM1). HDACs also coordinate fibroblast pro-inflammatory programs inducing leukemia inhibitory factor (LIF) expression, supporting paracrine pro-tumorigenic crosstalk. HDAC depletion in cancer-associated fibroblasts (CAFs) and treatment with the HDAC inhibitor entinostat (Ent) in PDAC mouse models reduce stromal activation and curb tumor progression. Notably, HDAC inhibition (HDACi) enriches a lipogenic fibroblast subpopulation, a potential precursor for myofibroblasts in the PDAC stroma. Overall, our study reveals the stromal targeting potential of HDACi, highlighting the utility of this epigenetic modulating approach in PDAC therapeutics.

cancer biology↗

bioRxiv2023

Metagenomic analysis of individual mosquitos reveals the ecology of insect viruses

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Using a meta-transcriptomic approach, we analysed the virome of 2,438 individual mosquitos (79 species), spanning [~]4000 km along latitudes and longitudes in China. From these data we identified 393 core viral species associated with mosquitos, including seven (putative) arbovirus species. We identified potential species and geographic hotspots of viral richness and arbovirus occurrence, and demonstrated that host phylogeny had a strong impact on the composition of individual mosquito viromes. Our data revealed a large number of viruses shared among mosquito species or genera, expanding our knowledge of host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, possibly facilitated by long-distance mosquito migrations. Together, our results greatly expand the known mosquito virome, linked the viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the ecology of viruses of insect vectors.

ecology↗

bioRxiv2023

CLOCK Mediates Delay in Cardiac Myofibroblast Formation and Attenuates Progression of Myocardial Fibrosis through Inhibition of Smad 3 Transcriptional Activity

IntroductionMyocardial fibrosis, characterized by excessive extracellular matrix deposition, leading to adverse cardiac remodeling and impaired function. The differentiation of cardiac fibroblasts into myofibroblasts plays a pivotal role in this process. The involvement of the core clock protein CLOCK in the formation of cardiac myofibroblasts and the advancement of myocardial fibrosis is not well understood. This study aims to investigate how CLOCK modulates cardiac myofibroblast differentiation and attenuates myocardial fibrosis by inhibiting Smad3 transcriptional activity. MethodsIn vivo, adeno-associated virus 9 was utilized for overexpression or silencing of the CLOCK gene via mice intravenous injection. In vitro experiments were conducted using primary cultures of cardiac fibroblasts isolated from mouse hearts to examine the expression levels of molecular markers associated with myofibroblast differentiation, such as -smooth muscle actin (-SMA) and collagen I. Additionally, a Smad3 luciferase reporter gene experiment was employed to assess the transcriptional activity of Smad3 under CLOCK regulation. ResultsThe results demonstrate that CLOCK overexpression significantly reduces the expression of -SMA and collagen I in cardiac fibroblasts, indicating a suppression of myofibroblast formation. Conversely, CLOCK knockdown enhances the expression of these fibrotic markers. Interestingly, CLOCK was found to negatively regulate the transcriptional activity of Smad3, suggesting a potential mechanism by which CLOCK exerts its inhibitory effect on cardiac fibrosis. Specifically, CLOCK interacts with Smad3, inhibiting its nuclear translocation and subsequent activation of fibro genic gene expression. ConclusionThese findings highlight the crucial role of CLOCK in the regulation of cardiac myofibroblast formation and the progression of myocardial fibrosis. CLOCK appears to exert an inhibitory effect on fibrotic signaling pathways, partially through the inhibition of Smad3 transcriptional activity. This study provides novel insights into the molecular mechanisms underlying cardiac fibrosis and emphasizes the therapeutic potential of targeting CLOCK-mediated pathways for treating myocardial fibrosis.

molecular biology↗

bioRxiv2022

The MOV10 RNA helicase is a dosage-dependent host restriction factor for LINE1 retrotransposition in mice

Transposable elements constitute nearly half of the mammalian genome and play important roles in genome evolution. While a multitude of both transcriptional and post-transcriptional mechanisms exist to silence transposable elements, control of transposition in vivo remains poorly understood. MOV10, an RNA helicase, is a potent inhibitor of mobilization of retrotransposons and retroviruses in cell culture assays. Here we report that MOV10 restricts LINE1 retrotransposition in mice. Although MOV10 is broadly expressed, its loss causes only incomplete penetrance of embryonic lethality, and the surviving MOV10-deficient mice are healthy and fertile. Biochemically, MOV10 forms a complex with UPF1, a key component of the nonsense-mediated mRNA decay pathway, and primarily binds to the 3UTR of somatically expressed transcripts in testis. Consequently, loss of MOV10 results in an altered transcriptome and a modest upregulation of two LINE1 families in testis. Analyses using a LINE1 reporter transgene reveal that loss of MOV10 leads to increased LINE1 retrotransposition in somatic and reproductive tissues from both embryos and adult mice. Moreover, the degree of LINE1 retrotransposition inhibition is dependent on the Mov10 gene dosage. Furthermore, MOV10 deficiency reduces reproductive fitness over successive generations. Our findings demonstrate that MOV10 attenuates LINE1 retrotransposition in a dosage-dependent manner in mice. Author summaryTransposable elements (TEs), including L1 and SINEs, are abundant in the genome and play important roles in evolution, development, and diseases. While TEs propagate in individuals and across generations, the host organism needs to suppress them, resulting in an ongoing arms race between TEs and the host genome. L1, a retrotransposon, accounts for about 17% of the mammalian genome. L1 encodes two proteins, which bind to the L1 transcript to form L1 ribonucleoprotein particles. L1 proliferates in the genome via retrotransposition. A multitude of transcriptional and post-transcriptional mechanisms exist to suppress TEs, however, retrotransposition of TEs remains poorly understood. L1 ribonucleoprotein particles are associated with a large number of host proteins, one of which is the MOV10 RNA helicase. MOV10 exhibits anti-viral activities against retroviruses such as HIV-1. In cultured cells, MOV10 is a potent inhibitor of retrotransposition of L1, SINEs, and IAP. Although MOV10 is expressed in a broad range of tissues, loss of MOV10 causes only incomplete penetrance of embryonic lethality. The viable MOV10-deficient mice are grossly normal and fertile. Importantly, analyses using a L1 transgene reporter reveal that MOV10 inhibits L1 retrotransposition in both somatic tissues and reproductive tissues in a gene dosage-dependent manner. Therefore, MOV10 functions as a host restriction factor for L1 and possibly other transposable elements in vivo.

developmental biology↗

bioRxiv2022

Individual bat viromes reveal the co-infection, spillover and emergence risk of potential zoonotic viruses

Bats are reservoir hosts for many zoonotic viruses. Despite this, relatively little is known about the diversity and abundance of viruses within bats at the level of individual animals, and hence the frequency of virus co-infection and inter-species transmission. Using an unbiased meta-transcriptomics approach we characterised the mammalian associated viruses present in 149 individual bats sampled from Yunnan province, China. This revealed a high frequency of virus co-infection and species spillover among the animals studied, with 12 viruses shared among different bat species, which in turn facilitates virus recombination and reassortment. Of note, we identified five viral species that are likely to be pathogenic to humans or livestock, including a novel recombinant SARS-like coronavirus that is closely related to both SARS-CoV-2 and SARS-CoV, with only five amino acid differences between its receptor-binding domain sequence and that of the earliest sequences of SARS-CoV-2. Functional analysis predicts that this recombinant coronavirus can utilize the human ACE2 receptor such that it is likely to be of high zoonotic risk. Our study highlights the common occurrence of inter-species transmission and co-infection of bat viruses, as well as their implications for virus emergence.

microbiology↗

bioRxiv2022

Cost-efficient boundary-free surface patterning achieves high effective-throughput of time-lapse microscopy experiments

Time-lapse microscopy plays critical roles in the studies of cellular dynamics. However, to set up a time-lapse movie experiments is not only laborious but also with low output, mainly due to the cell-losing problem (i.e., cell moving out of limited field of view), especially in a long time recording. To overcome these issues, we have designed a cost-efficient way that enables cell patterning on the imaging surfaces without any physical boundaries. Using mouse embryonic stem cells as an example system, we have demonstrated that our boundary-free patterned surface solves the cell-losing problem without disturbing their cellular phenotype. Statistically, the presented system increases the effective-throughput of time-lapse microscopy experiments by order of magnitude.

bioengineering↗

bioRxiv2022

IRONMAN interacts with OsHRZ1 and OsHRZ2 to maintain Fe homeostasis

IRONMAN is a family of small peptides which positively regulate the Fe deficiency response. However, the molecular mechanism by which OsIMA1 and OsIMA2 regulate Fe homeostasis was unclear. Here, we reveal that OsIMA1 and OsIMA2 interact with the potential Fe sensors, OsHRZ1 and OsHRZ2. OsIMA1 and OsIMA2 contain a conserved 17-amino acid C-terminal region which is responsible for the interactions with OsHRZ1 and OsHRZ2. The OsIMA1 overexpressing plants have the increased seed Fe concentration and the reduced fertility, as observed in the hrz1-2 loss-of-function mutant plants. Moreover, the expression trends of Fe deficiency inducible genes in the OsIMA1 overexpressing plants are the same to those in the hrz1-2. Co-expression assays suggest that OsHRZ1 and OsHRZ2 promote the degradation of OsIMA1 proteins. As the interaction partners of OsHRZ1, the OsPRI proteins also interact with OsHRZ2. The conserved C-terminal region of four OsPRIs contributes to the interactions with OsHRZ1 and OsHRZ2. An artificial IMA (aIMA) derived from the C-terminal of OsPRI1 can be also degraded by OsHRZ1. Moreover, the aIMA overexpressing rice plants accumulate more Fe without reduction of fertility. This work establishes the link between OsIMAs and OsHRZs, and develops a new strategy for Fe fortification in rice.

molecular biology↗

bioRxiv2022

POPEYE directly regulates bHLH Ib genes and its own expression

Iron (Fe) is an essential trace element for plants. When suffering from Fe deficiency, plants modulate the expression of Fe deficiency responsive genes. POPEYE (PYE) is a key bHLH transcription factor involved in Fe homeostasis. However, the molecular mechanism of PYE regulating the Fe deficiency response remains elusive. We found that the over-expression of PYE attenuates the expression of Fe deficiency responsive genes. PYE directly represses the transcription of bHLH Ib genes (bHLH38, bHLH39, bHLH100, and bHLH101) by associating with their promoters. Although PYE contains an Ethylene response factor-associated Amphiphilic Repression (EAR) motif, it does not interact with the transcriptional corepressors TOPLESS/TOPLESS-RELATED (TPL/TPRs). Subcellular localization analysis indicated that PYE localizes in both the cytoplasm and nucleus. PYE contains a Nuclear Export Signal (NES) which is required for the cytoplasmic localization of PYE. The mutation of NES amplifies the repression function of PYE, resulting in downregulation of Fe deficiency responsive genes. Co-expression assays indicated that bHLH IVc members (bHLH104, bHLH105/ILR3, and bHLH115) facilitate the nuclear accumulation of PYE. Conversely, PYE indirectly represses transcription activation ability of bHLH IVc. Additionally, PYE directly negatively regulates its own transcription. This study provides insights into the complicated Fe deficiency response signaling pathway and enhances the understanding of PYE functions. Short summaryPYE is a negative regulator of Fe homeostasis; however, it was still unclear how PYE integrates the Fe deficiency response signaling. Our study shows that conditional nuclear localization of PYE is crucial for Fe homeostasis. PYE not only negatively regulates FIT-dependent Fe uptake genes by directly targeting bHLH Ib genes, but also negatively regulates its own expression.

molecular biology↗

bioRxiv2022

OsIRO3 negatively regulates Fe homeostasis by repressing the expression of OsIRO2

Iron (Fe) is crucial for crop productivity and quality. However, Fe deficiency is prevalent worldwide, especially in alkaline soil. Plants have evolved sophisticated mechanisms to withstand Fe deficiency conditions. Oryza sativa IRON-RELATED BHLH TRANSCRIPTION FACTOR 3 (OsIRO3/OsbHLH63) has been identified as a negative regulator of Fe deficiency response signaling, however, the underlying mechanism remains unclear. In the present study, we constructed two iro3 mutants which generated leaves with necrotic lesions under Fe deficient conditions. Loss-of-function of OsIRO3 caused upregulation of Fe deficiency-associated genes in the root under Fe deficient conditions. Fe concentration measurement showed that the iro3 mutants had increased shoot Fe concentration only under Fe deficient conditions. Further analysis revealed that OsIRO3 directly regulated the expression of IRON-RELATED BHLH TRANSCRIPTION FACTOR 2 (OsIRO2) which encodes a positive regulator of Fe uptake system. Protein interaction tests indicated that OsIRO3 interacted with OsPRI1 and OsPRI2. Further investigation demonstrated that OsIRO3 repressed the transactivation of OsPRI1 and OsPRI2 towards OsIRO2. OsIRO3 contains an EAR motif which recruits the TOPLESS/TOPLESS-RELATED (OsTPL/OsTPRs) corepressors. Mutation of the EAR motif attenuated the repression ability of OsIRO3. This work sheds light on the molecular mechanism by which OsIRO3 modulates Fe homeostasis in rice.

plant biology↗

bioRxiv2022

Why FIT and bHLH Ib interdependently regulate Fe-uptake

FIT (FER-LIKE IRON DEFICIENCY- INDUCED TRANSCRIPTION FACTOR) and four bHLH Ib transcription factors (TFs) bHLH38, bHLH39, bHLH100 and bHLH101, are the master regulators of Fe uptake genes, and they interact with each other to activate the Fe uptake systems. However, it remains unclear why FIT and bHLH Ib depend on each other to regulate the Fe deficiency response. By analyzing Fe deficiency phenotypes and Fe uptake genes, we found that the quadruple bhlh4x mutants (bhlh38 bhlh39 bhlh100 bhlh101) mimic the fit mutant. Subcellular localization analyses indicate that bHLH38 and bHLH39 are preferentially expressed in the cytoplasm whereas bHLH100 and bHLH101 in the nucleus. Transcriptome data show that the genes involved in Fe signaling pathway show the same expression trends in bhlh4x and fit. Genetic analyses suggest that FIT and bHLH Ib depend each other to regulate the Fe deficiency response. Further biochemical assays indicate that bHLH Ib TFs possess the DNA binding ability and FIT has the transcription activation ability. This work concludes that FIT and bHLH Ib form a functional transcription complex in which bHLH Ib is responsible for target recognition and FIT for transcription activation, explaining why FIT and bHLH Ib interdependently regulate Fe uptake.

molecular biology↗

bioRxiv2021

Dehalobium species implicated in 2,3,7,8-tetrachloro-p-dioxin dechlorination in the contaminated sediments of Sydney Harbour Estuary

Polychlorinated dibenzo-p-dioxins and furans (PCDD/F) are some of the most environmentally recalcitrant and toxic compounds. They are naturally occurring and by-products of anthropogenic activity. Sydney Harbour Estuary (Sydney, Australia), is heavily contaminated with PCDD/F. Analysis of sediment cores revealed that the contamination source in Homebush Bay continues to have one of the highest levels of PCDD/F contamination in the world (5207 pg WHO-TEQ g-1) with >50% of the toxicity attributed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) the most toxic and concerning of the PCDD/F congeners. Comparison of congener profiles at the contamination source with surrounding bays and historical data provided evidence for the attenuation of 2,3,7,8-TCDD and other congeners at the source. This finding was supported by the detection of di-, mono- and unchlorinated dibenzo-p-dioxin. Microbial community analysis of sediments by 16S amplicon sequencing revealed an abundance of lineages from the class Dehalococcoidia (up to 15% of the community), including the genus Dehalobium (up to 0.5%). Anaerobic seawater enrichment cultures using perchloroethene as a more amenable growth substrate enriched only the Dehalobium population by more than six-fold. The enrichment culture then proved capable of reductively dechlorinating 2,3,7,8-TCDD to 2,3,7-TCDD and octachlorodibenzo-p-dibenzodioxin to hepta and hexa congeners. This work is the first to show microbial reductive dehalogenation of 2,3,7,8-TCDD with a bacterium from outside the Dehalococcoides genus, and one of only a few that demonstrates PCDD/F degradation in a marine environment.

microbiology↗

bioRxiv2021

Molecular recording of sequential cellular events into DNA

Genetically encoded DNA recorders noninvasively convert transient biological events into durable mutations in a cells genome, allowing for the later reconstruction of cellular experiences using high-throughput DNA sequencing1. Existing DNA recorders have achieved high-information recording2-15, durable recording3,5-10,13,15-19, multiplexed recording of several cellular signals5-8,19,20, and temporally resolved signal recording5-8,19,20, but not all at the same time in mammalian cells. We present a DNA recorder called peCHYRON (prime editing21 Cell HistorY Recording by Ordered iNsertion) that does. In peCHYRON, mammalian cells are engineered to express prime editor and a collection of prime editing guide RNAs21 (pegRNAs) that facilitate iterative rounds of prime editing. In each round of editing, prime editor inserts a variable triplet DNA sequence alongside a constant propagator sequence that deactivates the previous and activates the next step of insertion. Editing can continue indefinitely because each insertion adds the complete sequence needed to initiate the next step. Because only one active target site is present at any given time, insertions accumulate sequentially, in a unidirectional order. Thus, temporal information is preserved in the order of insertions. Durability is achieved through the use of a prime editor that only nicks a single DNA strand, effectively avoiding deletion mutations that could otherwise corrupt the information stored at the recording locus. High-information content is established by co-expressing a variety of pegRNAs, each harboring unique triplet DNA sequences. We demonstrate that constitutive expression of such a library of pegRNAs generates insertion patterns that support straightforward reconstruction of cell lineage relationships. In an alternative pegRNA expression scheme, we also achieve multiplexed recording by manually pulsing expression of different pegRNAs, then reconstructing pulse sequences from the peCHYRON records. Additionally, we coupled the expression of specific pegRNAs to specific biological stimuli, which allowed temporally resolved, multiplexed recording of chemical exposures in populations of mammalian cells. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=96 SRC="FIGDIR/small/467507v2_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@3dcbb2org.highwire.dtl.DTLVardef@1081b72org.highwire.dtl.DTLVardef@141fed3org.highwire.dtl.DTLVardef@1c0e8ef_HPS_FORMAT_FIGEXP M_FIG C_FIG

genetics↗

bioRxiv2021

Precise annotation of Drosophila mitochondrial genomes leads to insights into AT-rich regions

In the present study, we performed precise annotation of Drosophila melanogaster, D. simulans, D. grimshawi, Bactrocera oleae mitochondrial (mt) genomes by pan RNA-seq analysis. Our new annotations corrected or modified some of the previous annotations and two important findings were reported for the first time, including the discovery of the conserved polyA(+) and polyA(-) motifs in the control regions (CRs) of insect mt genomes and the adding of CCAs to the 3 ends of two antisense tRNAs in D. melanogaster mt genome. Using PacBio cDNA-seq data from D. simulans, we precisely annotated the Transcription Initiation Sites (TISs) of the mt Heavy and Light strands in Drosophila mt genomes and reported that the polyA(+) and polyA(-) motifs in the CRs are associated with TISs. The discovery of the conserved polyA(+) and polyA(-) motifs provides insights into many polyA and polyT sequences in CRs of insect mt genomes, leading to reveal the mt transcription and its regulation in invertebrates. In addition, we provided a high-quality, well-curated and precisely annotated D. simulans mt genome (GenBank: MN611461), which should be included into the NCBI RefSeq database to replace the current reference genome NC_005781.

bioinformatics↗

bioRxiv2021

Multi-Modal Data Analysis for Alzheimer's Disease Diagnosis: An Ensemble Model Using Imagery and Genetic Features

Alzheimers disease (AD) is a devastating neurological disorder primarily affecting the elderly. An estimated 6.2 million Americans age 65 and older are suffering from Alzheimers dementia today. Brain magnetic resonance imaging (MRI) is widely used for the clinical diagnosis of AD. In the meanwhile, medical researchers have identified 40 risk locus using single-nucleotide polymorphisms (SNPs) information from Genome-wide association study (GWAS) in the past decades. However, existing studies usually treat MRI and GWAS separately. For instance, convolutional neural networks are often trained using MRI for AD diagnosis. GWAS and SNPs are frequently used to identify genomic traits. In this study, we propose a multi-modal AD diagnosis neural network that uses both MRIs and SNPs. The proposed method demonstrates a novel way to use GWAS findings by directly including SNPs in predictive models. We test the proposed methods on the Alzheimers Disease Neuroimaging Initiative dataset. The evaluation results show that the proposed method improves the model performance on AD diagnosis and achieves 93.5% AUC and 96.1% AP, respectively, when patients have both MRI and SNP data. We believe this work brings exciting new insights to GWAS applications and sheds light on future research directions.

neuroscience↗

bioRxiv2020

bHLH11 negatively regulates Fe homeostasis by its EAR motifs recruiting corepressors in Arabidopsis

Iron (Fe) homeostasis is essential for plant growth and development. Many transcription factors play pivotal roles in the maintenance of Fe homeostasis. bHLH11 was identified as a negative transcription factor regulating Fe homeostasis, however, the underlying molecular mechanism remains elusive. We generated two loss-of-function bhlh11 mutants which display the enhanced sensitivity to Fe excess, the increased Fe accumulation and the elevated expression of Fe deficiency responsive genes. bHLH11 protein, localized in both the cytoplasm and nucleus, decreases in response to Fe deficiency. Coexpression assays indicate that bHLH IVc transcription factors (TFs) (bHLH34, bHLH104, bHLH105, and bHLH115) facilitate the nuclear accumulation of bHLH11 protein. Further analysis indicates that bHLH11 represses the transactivity of bHLH IVc TFs towards bHLH Ib genes (bHLH38, bHLH39, bHLH100, and bHLH101). bHLH11 contains two EAR motifs which are responsible for the repression function by recruiting the TOPLESS/TOPLESS-RELATED (TPL/TPRs) corepressors. Correspondingly, the expression of Fe uptake genes increases in the tpr1 tpr4 tpl mutant. Moreover, genetic analysis reveals that bHLH11 has functions independent of FIT. This study provides insights into the complicate Fe homeostasis signaling network. One-sentence summarybHLH IVc proteins promote the bHLH11 protein accumulation in the nucleus where bHLH11 inhibits the transcriptional activation ability of bHLH IVc via its EAR motifs recruiting the TOPLESS/TOPLESS-RELATED corepressors.

plant biology↗

bioRxiv2020

FER-LIKE FE DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (OsFIT) interacts with OsIRO2 to regulate iron homeostasis

There are two Fe-uptake strategies for maintaining Fe homeostasis in plants. As a special graminaceous plant, rice applies both strategies. However, it remains unclear how these two strategies are regulated in rice. IRON-RELATED BHLH TRANSCRIPTION FACTOR 2 (OsIRO2) is critical for regulating Fe uptake in rice. In this study, we identified an interacting partner of OsIRO2, Oryza sativa FER-LIKE FE DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (OsFIT), which encodes a bHLH transcription factor. The OsIRO2 protein is localized in the cytoplasm and nucleus, but OsFIT facilitates the accumulation of OsIRO2 in the nucleus. Loss-of-function mutations to OsFIT result in decreased Fe accumulation, severe Fe-deficiency symptoms, and disrupted expression of Fe-uptake genes. In contrast, OsFIT overexpression promotes Fe accumulation and the expression of Fe-uptake genes. Genetic analyses indicated that OsFIT and OsIRO2 function in the same genetic node. Further analysis suggested that OsFIT and OsIRO2 form a functional transcription activation complex to initiate the expression of Fe-uptake genes. Our findings provide a mechanism understanding of how rice maintains Fe homeostasis. One-sentence summaryOsFIT interacts with and facilitates the accumulation of OsIRO2 in the nucleus where the OsFIT-OsIRO2 transcription complex initiates the transcription of Fe deficiency responsive genes.

plant biology↗

bioRxiv2019

Distinct molecular processes in placentae involved in two major subtypes of preeclampsia

Patients with preeclampsia display a spectrum of onset time and severity of clinical presentation, yet the underlying molecular bases for the early-onset and late-onset clinical subtypes are not known. Since the root cause of PE is thought to be located in the placentae, we carried out RNA-seq on 65 high-quality placenta samples, including 33 from 30 patients and 32 from 30 control subjects, to search for molecular features. We identified two functionally distinct sets of dysregulated genes in two major subtypes: metabolism-related genes, notably transporter genes, in early-onset severe preeclampsia and immune-related genes in late-onset severe preeclampsia, while the late-onset mild preeclampsia could not be distinguished from normal controls. A small number of dysregulated transcription factors may drive the widespread gene dysregulation in both early-onset and late-onset patients. These results suggest that early-onset and late-onset severe preeclampsia have different molecular mechanisms, whereas the late-onset mild preeclampsia may have no placenta-specific causal factors.

genomics↗