GATA Factors Research Articles

GATA factor TRPS1, a new DNA repair protein, cooperates with reversible PARylation to promote chemoresistance in patients with breast cancer

Resistance to DNA-damaging agents is a major unsolved challenge for breast cancer patients undergoing chemotherapy. Here, we show that elevated expression of transcriptional repressor GATA binding 1 (TRPS1) is associated with lower drug sensitivity, reduced response rate, and poor prognosis in chemotherapy-treated breast cancer patients. Mechanistically, elevated TRPS1 expression promotes hyperactivity of DNA damage repair (DDR) in breast cancer cells. We provide evidence that TRPS1 dynamically localizes to DNA breaks in a Ku70- and Ku80-dependent manner, and that TRPS1 is a new member of the DDR protein family. We also discover that the dynamics of TRPS1 assembly at DNA breaks is regulated by its reversible PARylation in the DDR, and that mutations of the PARylation sites on TRPS1 lead to increased sensitivity to chemotherapeutic drugs. Taken together, our findings provide new mechanistic insights into the DDR and chemoresistance in breast cancer patients and identify TRPS1 as a critical DDR protein. TRPS1 may also be considered as a target to improve chemo-sensitization strategies and, consequently, clinical outcomes for breast cancer patients.

Transcriptomic and Metabolomic Insights into ABA-Related Genes in Cerasus humilis under Drought Stress.

Cerasus humilis, a small shrub of the Cerasus genus within the Rosaceae family, is native to China and renowned for its highly nutritious and medicinal fruits, robust root system, and remarkable drought resistance. This study primarily employed association transcriptome and metabolome analyses to assess changes in abscisic acid (ABA) levels and identify key regulatory genes in C. humilis subjected to varying degrees of drought stress. Notably, we observed distinct alterations in transcription factors across different drought intensities. Specifically, our transcriptome data indicated noteworthy shifts in GATA, MYB, MYC, WRKY, C2H2, and bHLH transcription factor families. Furthermore, combined transcriptomic and metabolomic investigations demonstrated significant enrichment of metabolic pathways, such as 'Carbon metabolism', 'Biosynthesis of amino acids', 'Biosynthesis of cofactors', 'Phenylpropanoid biosynthesis', 'Starch and sucrose metabolism', and 'Plant hormone signal transduction' under moderate (Mod) or severe (Sev) drought conditions. A total of 11 candidate genes involved in ABA biosynthesis and signaling pathways were identified. The down-regulated genes included secoisolariciresinol dehydrogenase-like and PYL2. Conversely, genes including FAD-dependent urate hydroxylase-like, cytochrome P450 97B2, carotenoid cleavage dioxygenase 4 (CCD4), SnRK2.2, ABI 5-like protein 5, PP2C 51, and SnRK2.3, were up-regulated under Mod or Sev drought stress. This study lays the genetic foundation for ABA biosynthesis to enhance drought tolerance and provides genetic resources for plant genetic engineering and breeding efforts.

GATA family transcription factors in alga Chlamydomonas reinhardtii.

GATA family transcription factors (GATA-TFs) are metalloproteins that regulate many metabolic pathways. These conserved proteins recognize the consensus sequence (A/T)GATA(A/G) in the promoter regions of many genes and regulate their transcription in response to environmental signals. Currently, the study of GATA-TFs is of increasing interest. GATA genes and their proteins are most actively studied in vascular plants and fungi. Based on the results of numerous studies, it has been shown that GATA factors regulate the metabolic pathways of nitrogen and carbon, and also play a major role in the processes induced by light and circadian rhythms. In algae, GATA-TFs remain poorly studied, and information about them is scattered. In this work, all known data on GATA-TFs in the unicellular green alga Chlamydomonas reinhardtii has been collected and systematized. The genome of this alga contains 12 GATA coding genes. Using the phylogenetic analysis, we identified three classes of GATA factors in C. reinhardtii according to the structure of the zinc finger domain and showed their difference from the classification of GATA factors developed on vascular plants.

The GATA transcriptional program dictates cell fate equilibrium to establish the maternal–fetal exchange interface and fetal development

The placenta establishes a maternal-fetal exchange interface to transport nutrients and gases between the mother and the fetus. Establishment of this exchange interface relies on the development of multinucleated syncytiotrophoblasts (SynT) from trophoblast progenitors, and defect in SynT development often leads to pregnancy failure and impaired embryonic development. Here, we show that mouse embryos with conditional deletion of transcription factors GATA2 and GATA3 in labyrinth trophoblast progenitors (LaTPs) have underdeveloped placenta and die by ~embryonic day 9.5. Single-cell RNA sequencing analysis revealed excessive accumulation of multipotent LaTPs upon conditional deletion of GATA factors. The GATA factor-deleted multipotent progenitors were unable to differentiate into matured SynTs. We also show that the GATA factor-mediated priming of trophoblast progenitors for SynT differentiation is a conserved event during human placentation. Loss of either GATA2 or GATA3 in cytotrophoblast-derived human trophoblast stem cells (human TSCs) drastically inhibits SynT differentiation potential. Identification of GATA2 and GATA3 target genes along with comparative bioinformatics analyses revealed that GATA factors directly regulate hundreds of common genes in human TSCs, including genes that are essential for SynT development and implicated in preeclampsia and fetal growth retardation. Thus, our study uncovers a conserved molecular mechanism, in which coordinated function of GATA2 and GATA3 promotes trophoblast progenitor-to-SynT commitment, ensuring establishment of the maternal-fetal exchange interface.

Human Genetics of Truncus Arteriosus.

Integrated human genetics and molecular/developmental biology studies have revealed that truncus arteriosus is highly associated with 22q11.2 deletion syndrome. Other congenital malformation syndromes and variants in genes encoding TBX, GATA, and NKX transcription factors and some signaling proteins have also been reported as its etiology.

GATA factor-related hematopoietic neoplasms

GATA1, GATA2, and GATA3, collectively known as hematopoietic GATA factors, play a central role in the transcription factor network that governs hematopoietic homeostasis. Dysfunction of these factors leads to various hematopoietic disorders. Aberrant function of GATA1 factor, crucial in erythrocyte and megakaryocyte differentiation, not only causes anemia and thrombocytopenia, but also triggers erythroid leukemia and acute megakaryoblastic leukemia. Similarly, GATA2 factor expression is dynamic in the hematopoietic hierarchy, and dysfunction of GATA2 factor contributes not only to dysfunction of the myeloid and lymphoid lineages but also to the development of diverse hematopoietic neoplasms such as myelodysplastic syndromes, acute myeloid leukemia, and myeloproliferative neoplasms. GATA3, critical for T-lymphocyte differentiation, is relevant to lymphocytic leukemia. This review discusses hematopoietic disorders caused by aberrant GATA transcription functions, with a particular emphasis on hematopoietic malignancies.

Identification long non-coding RNAs, miRNAs and their targets in witches’ broom disease tolerance in cocoa (Theobroma cacao L.)

A large part of transcripts is non-coding, which is transcribed from junk DNA; long non-coding RNAs and micro-RNAs regulate theexpression levels of mRNAs. For the first time, we identified lncRNAs and miRNAs with their regulatory role in the disease toleranceof Theobroma cacao. In this study, about 2616 lncRNAs and 153 miRNAs were identified from 10 RNA-seq data representing healthyand witches’ broom diseased tissues of cocoa. Around 604 lncRNAs are differentially expressed among healthy and diseased tissues.LncRNAs targeted 9692 mRNAs; 8827 are cis-acting, and 765 are trans-acting. Among targeted mRNAs, 281 are disease resistance-related transcripts, and 211 transcription factors (TFs) belong to more than 50 TF families, which were found to be involved in the regulation of the disease tolerance process. The identified 153 miRNAs belong to 27 miR families, and around 5337 mRNAs are targeted by the miRNAs, among them 114 codes for TFs and 170 codes for disease resistance protein. Ethylene responsive factor, bHLH, WRKY, MYB, bZIP, GTE, GATA, and heat stress transcription factors are the dominant TFs targeted by lncRNAs, and miRNAs play vital roles in disease progression and tolerance. A total of 55 lncRNAs-miRNAs interacting pair is identified, which were working on endogenous target mimics (e-TMs) mechanism and influenced the expression of 955 mRNAs. The ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) biological pathway analysis reveal that ncRNAs and their targets mRNAs code for transcription factors and genes that are involved in the disease tolerance processes, including synthesis of disease resistance proteins, amino acids, antibiotics, intracellular proteins that directly or indirectly recognize pathogen effectors are essential for plant biotic stress condition. The present study provides lncRNA and miRNA-based regulatory insight into the genes governing disease progression and tolerance in cocoa.

Interconnections between DDX41-Dependent Post-Transcriptional and GATA Factor-Instigated Transcriptional Mechanisms That Govern Hematopoiesis

Heterozygous DDX41 germline mutations occur in familial myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) and acute erythroid leukemia (AEL). DDX41 encodes an RNA helicase that regulates RNA splicing, cGAS-Sting signaling in innate immunity, and maintains genome stability in erythropoiesis. We described the innovation of a facile genetic rescue system to compare RNA-regulatory activities of wild type and disease-associated DDX41 variants in engineered HoxB8-immortalized (hi) murine myeloid progenitor cells (hi-Ddx41+/+ and Ddx41+/- cells) (Kim et al., Leukemia 2023). We identified DDX41-regulated transcripts and membrane proteins as quantitative metrics of DDX41 activity that discriminate benign from pathogenic DDX41 alleles. As these transcripts and the cognate proteins were not known to be components of GATA2 genetic networks that govern hematopoietic stem/progenitor cell (HSPC) transitions, we hypothesized that DDX41 mechanisms in progenitors operate in parallel with or independent of GATA2 mechanisms. Considering the biological and pathological importance of DDX41 and many unanswered questions on how clinical variants impact DDX41 activity, we instituted studies to discover DDX41-regulated transcript isoforms. The datasets are being used to unveil how DDX41 controls cellular functions, how clinical variants derail mechanisms, and to establish interconnections or independence with GATA factor mechanisms. To develop a broader perspective, we extended the myeloid data by innovating a rescue system to analyze DDX41 structure/function in G1E-ER-GATA1 erythroblasts that express a conditionally active ER-GATA1 allele. We used CRISPR/Cas9 to generate Ddx41 +/- clonal lines that expressed ~50% lower levels of DDX41 protein. A comparable system is being generated in human HUDEP2 erythroid precursor cells. We compared DDX41 with two disease-associated germline variants: G173R and K331deletion. G1E-ER-GATA1- Ddx41 +/-cells were infected with retrovirus expressing GFP, or GFP and DDX41 (WT, G173R, or K331del), GFP + cells were sorted, and total RNA was analyzed by RNA-seq. Differential expression analysis revealed 138 Ddx41-regulated transcripts (P < 0.05), with 63 elevated and 75 decreased. Disease-associated variants failed to regulate these transcripts. To establish relationships between DDX41-regulated and GATA1-regulated transcripts in erythroblasts, we compared DDX41-regulated transcripts with our GATA1 transcriptomic data (Tanimura et al., EMBO Rep. 2016; Dev. Cell 2018; Liao et al., Cell Rep. 2020), which revealed 78 transcripts co-regulated by DDX41 and GATA1. The RNA analysis is being extended to the proteome. To investigate similarities between DDX41-dependent post-transcriptional and GATA1-dependent transcriptional mechanisms, we analyzed the genes encoding the 78 co-regulated transcripts using gene ontology and pathway analyses. The gene signatures included downregulation of apoptosis (p=0.0006). We are testing the hypothesis that DDX41 and GATA1 operate additively or synergistically to control levels of transcripts encoding apoptotic regulators in developing erythroblasts, thus establishing a balance between pro-apoptotic and anti-apoptotic factors. We compared myeloid and erythroid DDX41-regulated transcript datasets to identify common and cell type-specific DDX41-regulated transcripts. This analysis unveiled 11 transcripts that are DDX41-regulated in both systems. One transcript encodes CLK3, a member of Cdc2-like kinase family that phosphorylates splicing factors. DDX41 increased intron 3 retention in Clk3 mRNA in both systems. By quantifying exon-intron junctions, we demonstrated that DDX41 promoted intron 3 retention in hi- Ddx41 +/- cells 1.7-fold (P = 0.0002) and in G1E-ER-GATA1- Ddx41 +/- cells 3.3-fold (P = 0.0002). We are testing models to explain the functional significance of DDX41-regulated Clk3 intron retention and discovered DDX41 regulates intron retention at other loci. We are assessing how DDX41 controls alternative splicing globally in the erythroid and myeloid systems and elucidating the biological and pathological consequences of corrupting these mechanisms. In aggregate, these studies established a system to discriminate pathogenic from benign DDX41 variants, and mechanistic insights that provide the basis for new myeloid and erythroid paradigms.

A transcriptional network governing ceramide homeostasis establishes a cytokine-dependent developmental process

Transcriptional mechanisms controlling developmental processes establish and maintain proteomic networks, which can govern the levels of intracellular small molecules. Although dynamic changes in bioactive small molecules can link transcription factor and genome activity with cell state transitions, many mechanistic questions are unresolved. Using quantitative lipidomics and multiomics, we discover that the hematopoietic transcription factor GATA1 establishes ceramide homeostasis during erythroid differentiation by regulating genes encoding sphingolipid metabolic enzymes. Inhibiting a GATA1-induced sphingolipid biosynthetic enzyme, delta(4)-desaturase, or disrupting ceramide homeostasis with cell-permeable dihydroceramide or ceramide is detrimental to erythroid, but not myeloid, progenitor activity. Coupled with genetic editing-based rewiring of the regulatory circuitry, we demonstrate that ceramide homeostasis commissions vital stem cell factor and erythropoietin signaling by opposing an inhibitory protein phosphatase 2A-dependent, dual-component mechanism. Integrating bioactive lipids as essential components of GATA factor mechanisms to control cell state transitions has implications for diverse cell and tissue types.

GATA transcription factors drive initial Xist upregulation after fertilization through direct activation of long-range enhancers.

X-chromosome inactivation (XCI) balances gene expression between the sexes in female mammals. Shortly after fertilization, upregulation of Xist RNA from one X chromosome initiates XCI, leading to chromosome-wide gene silencing. XCI is maintained in all cell types, except the germ line and the pluripotent state where XCI is reversed. The mechanisms triggering Xist upregulation have remained elusive. Here we identify GATA transcription factors as potent activators of Xist. Through a pooled CRISPR activation screen in murine embryonic stem cells, we demonstrate that GATA1, as well as other GATA transcription factors can drive ectopic Xist expression. Moreover, we describe GATA-responsive regulatory elements in the Xist locus bound by different GATA factors. Finally, we show that GATA factors are essential for XCI induction in mouse preimplantation embryos. Deletion of GATA1/4/6 or GATA-responsive Xist enhancers in mouse zygotes effectively prevents Xist upregulation. We propose that the activity or complete absence of various GATA family members controls initial Xist upregulation, XCI maintenance in extra-embryonic lineages and XCI reversal in the epiblast.

Rice OsGATA16 is a positive regulator for chlorophyll biosynthesis and chloroplast development.

Chloroplasts are essential organelles in plants that contain chlorophylls and facilitate photosynthesis for growth and development. As photosynthetic efficiency significantly impacts crop productivity, understanding the regulatory mechanisms of chloroplast development has been crucial in increasing grain and biomass production. This study demonstrates the involvement of OsGATA16, an ortholog of Arabidopsis GATA, NITRATE INDUCIBLE, CARBON-METABOLISM INVOLVED (GNC), and GNC-LIKE/CYTOKININ-RESPONSIVE GATA FACTOR 1 (GNL/CGA1), in chlorophyll biosynthesis and chloroplast development in rice (Oryza sativa). The osgata16-1 knockdown mutants produced pale-green leaves, while OsGATA16-overexpressed plants (OsGATA16-OE1) generated dark-green leaves, compared to their parental japonica rice. Reverse transcription and quantitative PCR analysis revealed downregulation of genes related to chloroplast division, chlorophyll biosynthesis, and photosynthesis in the leaves of osgata16-1 and upregulation in those of OsGATA16-OE1. Additionally, in vivo binding assays showed that OsGATA16 directly binds to the promoter regions of OsHEMA, OsCHLH, OsPORA, OsPORB, and OsFtsZ, and upregulates their expression. These findings indicate that OsGATA16 serves as a positive regulator controlling chlorophyll biosynthesis and chloroplast development in rice.

Correction for Ling et al., Amino acid-dependent regulation of insulin-like peptide signaling is mediated by TOR and GATA factors in the disease vector mosquito Aedes aegypti.

Correction for Ling et al., Amino acid-dependent regulation of insulin-like peptide signaling is mediated by TOR and GATA factors in the disease vector mosquito Aedes aegypti.

Comprehensive Analysis and Characterization of the GATA Gene Family, with Emphasis on the GATA6 Transcription Factor in Poplar.

GATA transcription factors are ubiquitously present in eukaryotic organisms and play a crucial role in multiple biological processes, such as plant growth, stress response, and hormone signaling. However, the study of GATA factors in poplar is currently limited to a small number of proteins, despite their evident functional importance. In this investigation, we utilized the most recent genome annotation and stringent criteria to identify 38 GATA transcription factor genes in poplar. Subsequently, we conducted a comprehensive analysis of this gene family, encompassing phylogenetic classification, protein characterization, analysis of promoter cis-acting elements, and determination of chromosomal location. Our examination of gene duplication events indicated that both tandem and segmental duplications have contributed to the expansion of the GATA gene family in poplar, with segmental duplication potentially being a major driving force. By performing collinearity analysis of genes across six different species, we identified 74 pairs of co-linear genes, which provide valuable insights for predicting gene functions from a comparative genomics perspective. Furthermore, through the analysis of gene expression patterns, we identified five GATA genes that exhibited differential expression in leaf-stem-root tissues and eight genes that were responsive to salt stress. Of particular interest was GATA6, which displayed strong induction by salt stress and overlapped between the two gene sets. We discovered that GATA6 encodes a nuclear-localized protein with transcription activation activity, which is continuously induced by salt stress in leaf and root tissues. Moreover, we constructed a co-expression network centered around GATA6, suggesting the potential involvement of these genes in the growth, development, and response to abiotic stress processes in poplar through cell transport systems and protein modification mechanisms, such as vesicle-mediated transport, intracellular transport, ubiquitination, and deubiquitination. This research provides a foundation for further exploration of the functions and mechanisms of GATA transcription factors in poplar.

Amino acid–dependent regulation of insulin-like peptide signaling is mediated by TOR and GATA factors in the disease vector mosquito Aedes aegypti

Aedes aegypti female mosquitoes require vertebrate blood for their egg production and consequently they become vectors of devastating human diseases. Amino acids (AAs) and nutrients originating from a blood meal activate vitellogenesis and fuel embryo development of anautogenous mosquitoes. Insulin-like peptides (ILPs) are indispensable in reproducing female mosquitoes, regulating glycogen and lipid metabolism, and other essential functions. However, how ILPs coordinate their action in response to the AA influx in mosquito reproduction was unknown. We report here that the AA/Target of Rapamycin (TOR) signaling pathway regulates ILPs through GATA transcription factors (TFs). AA infusion combined with RNA-interference TOR silencing of revealed their differential action on ILPs, elevating circulating levels of several ILPs but inhibiting others, in the female mosquito. Experiments involving isoform-specific CRISPR-Cas9 genomic editing and chromatin immunoprecipitation assays showed that the expression of ilp4ilp6, and ilp7 genes was inhibited by the GATA repressor (GATAr) isoform in response to low AA-TOR signaling, while the expression of ilp1ilp2ilp3ilp5, and ilp8 genes was activated by the GATA activator isoform after a blood meal in response to the increased AA-TOR signaling. FoxO, a downstream TF in the insulin pathway, was involved in the TOR-GATAr-mediated repression of ilp4ilp6, and ilp7 genes. This work uncovered how AA/TOR signaling controls the ILP pathway in modulation of metabolic requirements of reproducing female mosquitoes.

Fluid shear stress-modulated chromatin accessibility reveals the mechano-dependency of endothelial SMAD1/5-mediated gene transcription

Bone morphogenetic protein (BMP) signaling and fluid shear stress (FSS) mediate complementary functions in vascular homeostasis and disease development. It remains to be shown whether altered chromatin accessibility downstream of BMP and FSS offers a crosstalk level to explain changes in SMAD-dependent transcription. Here, we employed ATAC-seq to analyze arterial endothelial cells stimulated with BMP9 and/or FSS. We found that BMP9-sensitive regions harbor non-palindromic GC-rich SMAD-binding elements (GGCTCC) and 69.7% of these regions become BMP-insensitive in the presence of FSS. While GATA and KLF transcription factor (TF) motifs are unique to BMP9- and FSS-sensitive regions, respectively, SOX motifs are common to both. Finally, we show that both SOX(13/18) and GATA(2/3/6) family members are directly upregulated by SMAD1/5. These findings highlight the mechano-dependency of SMAD-signaling by a sequential mechanism of first elevated pioneer TF expression, allowing subsequent chromatin opening to eventually providing accessibility to novel SMAD binding sites.

Baicalein mitigates oxidative stress and enhances lifespan through modulation of Wnt ligands and GATA factor: ELT-3 in Caenorhabditis elegans

AimsAge predispose individual to major diseases, and the biological processes contributing to aging are currently under intense investigation. Hence, plant-based natural compounds could be a potential target to counteract aging and age-associated diseases. So, the present study aims to investigate the antiaging properties of a natural compound Baicalein (BAI) on C. elegans and to elucidate the pathways or signaling molecules involved. MethodsHerein, we investigated the inhibitory effects of BAI on different Wnt ligands of C. elegans and its underlying mechanisms. Moreover, we monitored BAI's antiaging effect on the worms' lifespan and its different aging parameters. We employed different mutant and transgenic C. elegans strains to identify the pathways and transcription factors involved. Key findingsWe first showed that BAI could downregulate different Wnt ligands mRNA expressions in C. elegans, resulting in enhanced expression of GATA transcription factor ELT-3 and antiaging gene Klotho. On further evaluation, it was observed that BAI could enhance the worm's lifespan via ELT-3 and SKN-1 transcription factors, whereas, for the protection of worms against external oxidative stress, both ELT-3 and DAF-16 transcription factors were involved. Moreover, sensitive aging parameters of worms, including lipofuscin and ROS accumulation, and the declined physiological and mechanical functions observed in aged worms were ameliorated by BAI. SignificanceThis study highlighted BAI as a promising antiaging compound. This study also revealed the Wnt inhibitory potential of BAI with future implications for pharmacological target of age-associated diseases with aberrant activation of the Wnt pathway.

Evolutionary Change in Gut Specification in Caenorhabditis Centers on the GATA Factor ELT-3 in an Example of Developmental System Drift.

Cells in a developing animal embryo become specified by the activation of cell-type-specific gene regulatory networks. The network that specifies the gut in the nematode Caenorhabditis elegans has been the subject of study for more than two decades. In this network, the maternal factors SKN-1/Nrf and POP-1/TCF activate a zygotic GATA factor cascade consisting of the regulators MED-1,2 → END-1,3 → ELT-2,7, leading to the specification of the gut in early embryos. Paradoxically, the MED, END, and ELT-7 regulators are present only in species closely related to C. elegans, raising the question of how the gut can be specified without them. Recent work found that ELT-3, a GATA factor without an endodermal role in C. elegans, acts in a simpler ELT-3 → ELT-2 network to specify gut in more distant species. The simpler ELT-3 → ELT-2 network may thus represent an ancestral pathway. In this review, we describe the elucidation of the gut specification network in C. elegans and related species and propose a model by which the more complex network might have formed. Because the evolution of this network occurred without a change in phenotype, it is an example of the phenomenon of Developmental System Drift.

The role of GATA switch in benzene metabolite hydroquinone inhibiting erythroid differentiation in K562 cells.

The phenolic metabolite of benzene, hydroquinone (HQ), has potential risks for hematological disorders and hematotoxicity in humans. Previous studies have revealed that reactive oxygen species, DNA methylation, and histone acetylation participate in benzene metabolites inhibiting erythroid differentiation in hemin-induced K562 cells. GATA1 and GATA2 are crucial erythroid-specific transcription factors that exhibit dynamic expression patterns during erythroid differentiation. We investigated the role of GATA factors in HQ-inhibited erythroid differentiation in K562 cells. When K562 cells were induced with 40μM hemin for 0-120h, the mRNA and protein levels of GATA1 and GATA2 changed dynamically. After exposure to 40μM HQ for 72h, K562 cells were induced with 40μM hemin for 48h. HQ considerably reduced the percentage of hemin-induced Hb-positive cells, decreased the GATA1 mRNA, protein, and occupancy levels at α-globin and β-globin gene clusters, and increased the GATA2 mRNA and protein levels significantly. ChIP-seq analysis revealed that HQ reduced GATA1 occupancy, and increased GATA2 occupancy at most gene loci in hemin-induced K562 cells. And GATA1 and GATA2 might play essential roles in the erythroid differentiation protein interaction network. These results elucidate that HQ decreases GATA1 occupancy and increases GATA2 occupancy at the erythroid gene loci, thereby downregulating GATA1 and upregulating GATA2 expression, which in turn modulates the expression of erythroid genes and inhibits erythroid differentiation. This partially explains the mechanism of benzene hematotoxicity.

Arabidopsis thaliana B-GATA factors repress starch synthesis and gravitropic growth responses.

Plants perceive the direction of gravity during skotomorphogenic growth, and of gravity and light during photomorphogenic growth. Gravity perception occurs through the sedimentation of starch granules in shoot endodermal and root columella cells. In this study, we demonstrate that the Arabidopsis thaliana GATA factors GNC (GATA, NITRATE-INDUCIBLE, CARBON METABOLISM-INVOLVED) and GNL/CGA1 (GNC-LIKE/CYTOKININ-RESPONSIVE GATA1) repress starch granule growth and amyloplast differentiation in endodermal cells. In our comprehensive study, we analysed gravitropic responses in the shoot, root and hypocotyl. We performed an RNA-seq analysis, used advanced microscopy techniques to examine starch granule size, number and morphology and quantified transitory starch degradation patterns. Using transmission electron microscopy, we examined amyloplast development. Our results indicate that the altered gravitropic responses in hypocotyls, shoots and roots of gnc gnl mutants and GNL overexpressors are due to the differential accumulation of starch granules observed in the GATA genotypes. At the whole-plant level, GNC and GNL play a more complex role in starch synthesis, degradation and starch granule initiation. Our findings suggest that the light-regulated GNC and GNL help balance phototropic and gravitropic growth responses after the transition from skotomorphogenesis to photomorphogenesis by repressing the growth of starch granules.

Regulation of High-Affinity Iron Acquisition, Including Acquisition Mediated by the Iron Permease FtrA, Is Coordinated by AtrR, SrbA, and SreA in Aspergillus fumigatus.

Iron acquisition is crucial for virulence of the human pathogen Aspergillus fumigatus. Previous studies indicated that this mold regulates iron uptake via both siderophores and reductive iron assimilation by the GATA factor SreA and the SREBP regulator SrbA. Here, characterization of loss of function as well as hyperactive alleles revealed that transcriptional activation of iron uptake depends additionally on the Zn2Cys6 regulator AtrR, most likely via cooperation with SrbA. Mutational analysis of the promoter of the iron permease-encoding ftrA gene identified a 210-bp sequence, which is both essential and sufficient to impart iron regulation. Further studies located functional sequences, densely packed within 75 bp, that largely resemble binding motifs for SrbA, SreA, and AtrR. The latter, confirmed by chromatin immunoprecipitation (ChIP) analysis, is the first one not fully matching the 5'-CGGN12CCG-3' consensus sequence. The results presented here emphasize for the first time the direct involvement of SrbA, AtrR, and SreA in iron regulation. The essential role of both AtrR and SrbA in activation of iron acquisition underlines the coordination of iron homeostasis with biosynthesis of ergosterol and heme as well as adaptation to hypoxia. The rationale is most likely the iron dependence of these pathways along with the enzymatic link of biosynthesis of ergosterol and siderophores. IMPORTANCE Aspergillus fumigatus is the most common filamentous fungal pathogen infecting humans. Iron acquisition via siderophores has previously been shown to be essential for virulence of this mold species. Here, we demonstrate that AtrR, a transcription factor previously shown to control ergosterol biosynthesis, azole resistance, and adaptation to hypoxia, is essential for activation of iron acquisition, including siderophore biosynthesis and uptake. Dissection of an iron-regulated promoter identified binding motifs for AtrR and the two previously identified regulators of iron acquisition, SrbA and SreA. Altogether, this study identified a new regulator required for maintenance of iron homeostasis, revealed insights into promoter architecture for iron regulation, and emphasized the coordinated regulation of iron homeostasis ergosterol biosynthesis and adaptation to hypoxia.