Artemisia argyi is an important medicinal and economic plant in China, with the effects of warming channels, dispersing cold, and relieving pain, inflammation, and allergy. The essential oil of this plant is rich in volatile terpenoids and widely used in moxi-bustion and healthcare products, with huge market potential. The bZIP transcription factors compose a large family in plants and are involved in the regulation of plant growth and development, stress response, and biosynthesis of secondary metabolites such as terpenoids. However, little is known about the bZIPs and their roles in A. argyi. In this study, the bZIP transcription factors in the genome of A. argyi were systematically identified, and their physicochemical properties, phylogenetic relationship, conserved motifs, and promoter-binding elements were analyzed. Candidate AarbZIP genes involved in terpenoid biosynthesis were screened out. The results showed that a total of 156 AarbZIP transcription factors were identified at the genomic level, with the lengths of 99-618 aa, the molecular weights of 11.7-67.8 kDa, and the theoretical isoelectric points of 4.56-10.16. According to the classification of bZIPs in Arabidopsis thaliana, the 156 AarbZIPs were classified into 12 subfamilies, and the members in the same subfamily had similar conserved motifs. The cis-acting elements of promoters showed that AarbZIP genes were possibly involved in light and hormonal pathways. Five AarbZIP genes that may be involved in the regulation of terpenoid biosynthesis were screened out by homologous alignment and phylogenetic analysis. The qRT-PCR results showed that the expression levels of the five AarbZIP genes varied significantly in different tissues of A. argyi. Specifically, AarbZIP29 and AarbZIP55 were highly expressed in the leaves and AarbZIP81, AarbZIP130, and AarbZIP150 in the flower buds. This study lays a foundation for the functional study of bZIP genes and their regulatory roles in the terpenoid biosynthesis in A. argyi.
Gene Expression Profiling ; Phylogeny ; Artemisia/genetics* ; Basic-Leucine Zipper Transcription Factors/metabolism* ; Terpenes ; Gene Expression Regulation, Plant

Nutrient overload-caused deregulation of glucose and lipid metabolism leads to insulin resistance and metabolic disorders, which increases the risk of several types of cancers. CREB/ATF bZIP transcription factor (CREBZF), a novel transcription factor of the ATF/CREB family, has emerged as a critical mechanism bridging the gap between metabolism and cell growth. CREBZF forms a heterodimer with other proteins and functions as a coregulator for gene expression. CREBZF deficiency in the liver attenuates hepatic steatosis in high fat diet-induced insulin-resistant mice, while the expression levels of CREBZF are increased in the livers of obese mice and humans with hepatic steatosis. Intriguingly, CREBZF also regulates cell proliferation and apoptosis via interaction with several transcription factors including STAT3, p53 and HCF-1. Knockout of CREBZF in hepatocytes results in enhanced cell cycle progression and proliferation capacity in mice. Here we highlight how the CREBZF signaling network contributes to the deregulation of metabolism and cell growth, and discuss the potential of targeting these molecules for the treatment of insulin resistance, diabetes, fatty liver disease and cancer.
Animals ; Basic-Leucine Zipper Transcription Factors/metabolism* ; Cell Cycle ; Cell Proliferation ; Diet, High-Fat ; Hepatocytes ; Insulin Resistance ; Lipid Metabolism ; Liver ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Signal Transduction

OBJECTIVE: To determine the time course and potential mechanism of fibroblast growth factor-1 (FGF-1) in the regulation of adipogenesis.
 METHODS: We cultured human Simpson-Golabi-Behmel syndrome (SGBS) pre-adipocytes with recombinant FGF-1 and harvested cells at various stages prior to and during differentiation; at cell proliferation (D-3), confluence (D0), early (D3), middle (D7) and mature (D14) stages of differentiation. We determined lipid accumulation in mature adipocytes by morphological observation and quantitative measurement of oil red O staining. We also examined the expression of adipogenic genes and related markers involved in the Wnt/β-catenin pathway using quantitative Real-time PCR and Western blot.
 RESULTS: Compared to control SGBS cells, treatment with FGF-1 increased lipid accumulation; induced a sustained increase in the mRNA for peroxisome proliferater-activated receptor γ (PPARγ), glyceraldehyde-3-phosphate dehydrogenase (G3PDH), adiponectin and glucose transporter type 4 (GLUT4); and promoted a sustained decrease in expression of markers of the Wnt/β-catenin pathway, β-catenin and transcription factor 4 (TCF4).
 CONCLUSION The adipogenic effects of FGF-1 are apparent throughout the whole priming and differentiation period in human SGBS pre-adipocytes. Furthermore, our results suggest that FGF-1 
promotes adipogenesis, at least in part, via a sustained decrease in activity of the Wnt/β-catenin pathway.
Adipocytes ; drug effects ; metabolism ; Adipogenesis ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; metabolism ; Cell Differentiation ; Cells, Cultured ; Fibroblast Growth Factor 1 ; pharmacology ; Humans ; Recombinant Proteins ; pharmacology ; Transcription Factor 4 ; Transcription Factors ; metabolism ; Wnt Signaling Pathway ; beta Catenin ; metabolism

TCF4 (transcription factor 4; E2-2, ITF2) is a transcription factor that when haplo-insufficient causes Pitt-Hopkins Syndrome (PTHS), an autism-spectrum disorder that is associated with pervasive developmental delay and severe intellectual disability. The TCF4 gene is also a risk factor with highly significant linkage to schizophrenia, presumably via overexpression of the TCF4 gene product in the central nervous system. This review will present an overview of the clinical manifestations of PTHS and relate those clinical attributes to the underlying molecular genetics of TCF4. In order to provide a molecular biological context for the loss of function of TCF4 in PTHS, the review will also present a brief overview of the basic biochemistry of TCF4-mediated regulation of cellular and neuronal gene expression. In the final section of this review, I will discuss and speculate upon possible roles for the TCF4 transcription factor in neuronal function and comment upon how understanding these roles may give new insights into the molecular neurobiology of human cognition.
Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics/*metabolism ; Disease Models, Animal ; Facies ; Humans ; Hyperventilation/diagnosis/*genetics/pathology ; Intellectual Disability/diagnosis/*genetics/pathology ; Neurons/metabolism/pathology ; *Transcription, Genetic

To clarify the function and molecular mechanism of miR-155 in myogenic differentiation of C2C12, we constructed adenovirus over-expression vector of miR-155, then C2C12 cells were infected by adenovirus and induced myogenic differentiation. First, we observed the morphology of C2C12 after differentiation. Then the mRNA and protein expressions of myogenic markers (MyoD, MyoG and MyHC) were detected by qPCR and western blotting. Subsequently, the dual luciferase reporter gene assay was carried out to validate putative target gene (TCF4) of miR-155. Meanwhile, mRNA level of TCF4 was analyzed after over-expressing miR-155. The results show that over-expressed miR-155 reduced myotubes formation. Moreover, the mRNA and protein expression of MyoG and MyHC decreased significantly (P < 0.01). Further research demonstrated miR-155 bound the one (4532-4538) of three putative sites (1487-1493,1516-1522, 4532-4583) of TCF4 by luciferase reporter gene assay and the mRNA level of TCF4 decreased notably (P < 0.05). The data suggest that miR-155 inhibited myogenic differentiation of C2C12 through targeted TCF4.
Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; genetics ; Cell Differentiation ; Cell Line ; Genetic Vectors ; Mice ; MicroRNAs ; genetics ; Myoblasts ; cytology ; Myogenin ; genetics ; metabolism ; Myosin Heavy Chains ; genetics ; metabolism ; RNA, Messenger ; genetics ; Transcription Factor 4

OBJECTIVESTo investigate the expression and clinical significance of BATF2 in the oral tongue squamous cell carcinoma (OTSCC).

METHODSExpression of BATF2 mRNA and protein in 16 paired OTSCC tissues and adjacent non-tumor mucosa were examined using quantitative PCR, western blotting analysis and immunohistochemistry assays, and the relation between BATF2 expression and clinical pathologic factor and prognosis was analyzed.

RESULTSIn 16 paired tissues, expression of BATF2 mRNA in 13 OTSCC tissues and expression of BATF2 protein in 14 OTSCC tissues were significantly lower than that in adjacent non-tumor mucosa. In 202 paraffin-embedded OTSCC samples, BATF2 was not expressed in 20 cases (9.9%), low expressed in 104 cases (51.5%) and highly expressed in 78 (38.6%). BATF2 expression level was significantly correlated with histological differentiation (P = 0.002). Patients with low BATF2 expression had significantly poorer overall survival and disease-free survival than those with high BATF2 expression (P < 0.001).

CONCLUSIONSBATF2 was low expressed in OTSCC and related to tumor differentiation and prognosis and may serve as a prognostic biomarker and potential therapeutic target for this disease.

Adult ; Aged ; Basic-Leucine Zipper Transcription Factors ; genetics ; metabolism ; Blotting, Western ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Mouth Mucosa ; metabolism ; Prognosis ; RNA, Messenger ; metabolism ; Tongue Neoplasms ; metabolism ; pathology

This study was aimed to investigate the regulatory mechanism of heat shock protein 90 (Hsp90) on transcription factor EB (TFEB) during autophagy in liver cancer cells. Human hepatocellular carcinoma cell line HepG2 was treated with Hsp90 N- and C-terminal inhibitors (STA9090 and Novobiocin), respectively. Western blot and RT-PCR were used to detect the expression levels of TFEB and autophagy-related proteins. Chromatin immunoprecipitation (ChIP) assay was used to observe the ability of Hsp90α binding to the TFEB proximal promoter region. The double-luciferase gene reporter experiment was used to determine the activity of TFEB promoter. The results showed that hypoxia induced up-regulation of TFEB protein and mRNA expression levels in the HepG2 cells. The protein expression levels of TFEB, LC3 and P62 were down-regulated significantly by either STA9090 or Novobiocin, under both normoxic and hypoxic conditions. Transfection of Hsp90α-overexpressing plasmids up-regulated TFEB protein levels in either wild-type or Hsp90α knockout HepG2 cells. Hsp90 bound to the TFEB proximal promoter region and was involved in regulating TFEB transcriptional process. Whereas both STA9090 and Novobiocin inhibited Hsp90 to bind to the TFEB proximal promoter region, and decreased the activity of TFEB promoter. These results suggest that Hsp90 promotes TFEB transcription in human hepatocellular carcinoma cells by binding to the proximal promoter region, thereby up-regulating the expression levels of autophagy-related proteins.
Autophagy ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; pathology ; HSP90 Heat-Shock Proteins ; metabolism ; Hep G2 Cells ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Promoter Regions, Genetic

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus demonstrated to be associated with human disease. Infection by the HTLV-1 can cause T-cell leukemia (ATL) in adults. HTLV-1 bZIP factor (HBZ) is a viral protein encoded by the minus strand of the HTLV-1 provirus. Among the regulatory and accessory genes of HTLV-1, HBZ is the only gene that remains intact and which is expressed consistently in all patients with ATL. Moreover, HBZ has a critical role in the leukemogenesis of ATL. Here, we review the function of HBZ in the oncogenesis of HTLV-1 and its molecular mechanism of action.
Animals ; Basic-Leucine Zipper Transcription Factors ; genetics ; metabolism ; Carcinogenesis ; HTLV-I Infections ; pathology ; virology ; Human T-lymphotropic virus 1 ; genetics ; metabolism ; Humans ; Leukemia, T-Cell ; pathology ; virology ; Retroviridae Proteins ; genetics ; metabolism

Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; genetics ; metabolism ; Diet, High-Fat ; Dietary Carbohydrates ; administration & dosage ; Dietary Fats ; administration & dosage ; Lipoproteins, IDL ; blood ; Liver ; metabolism ; Male ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Triglycerides ; blood

Astragaloside Ⅳ(AS-Ⅳ) has protective effects against ischemia-reperfusion injury(IRI), but its mechanism of action has not yet been determined. This study aims to investigate the protective effects and mechanism of AS-Ⅳ on H9c2 cardiomyocyte injury induced by hypoxia-reoxygenation(H/R). The H/R model of myocardial cells was established by hypoxic culture for 12 hours and then reoxygenation culture for 8 hours. After AS-Ⅳ treatment, cell viability, the reactive oxygen species(ROS) levels, as well as the content or activity of superoxide dismutase(SOD), malondialdehyde(MDA), interleukin 6(IL-6), and tumor necrosis factor alpha(TNF-α), were measured to evaluate the effect of AS-Ⅳ treatment. The effect of AS-Ⅳ on HO-1 protein expression and nuclear Nrf2 and Bach1 protein expression was determined by Western blot. Finally, siRNA was used to knock down HO-1 gene expression to observe its reversal effect on AS-Ⅳ intervention. The results showed that as compared with the H/R model group, the cell viability was significantly increased(P<0.01), ROS level in the cells, MDA, hs-CRP and TNF-α in cell supernatant and nuclear protein Bach1 expression in the cells were significantly decreased(P<0.01), while SOD content, HO-1 protein expression in cells and expression of nuclear protein Nrf2 were significantly increased(P<0.01) in H/R+AS-Ⅳ group. However, pre-transfection of HO-1 siRNA into H9c2 cells by liposome could partly reverse the above effects of AS-Ⅳ after knocking down the expression of HO-1. This study suggests that AS-Ⅳ has significant protective effect on H/R injury of H9c2 cardiomyocytes, and Nrf2/Bach1/HO-1 signaling pathway may be a key signaling pathway for the effect.
Apoptosis ; Basic-Leucine Zipper Transcription Factors ; metabolism ; Cell Hypoxia ; Cells, Cultured ; Heme Oxygenase-1 ; metabolism ; Humans ; Myocytes, Cardiac ; drug effects ; NF-E2-Related Factor 2 ; metabolism ; Saponins ; pharmacology ; Signal Transduction ; Triterpenes ; pharmacology