Estrogen receptor (ER) and progesterone receptor (PR) are two important members of steroid receptors family, an evolutionarily conserved family of transcription factors. Upon binding to their ligands, ER and PR enter cell nucleus to interact with specific DNA element in the context of chromatin to initiate the transcription of diverse target genes, which largely depends on the timely recruitment of a wide range of cofactors. Moreover, the interactions between steroid hormones and their respective receptors also trigger post-translational modifications on these receptors to fine-tune their transcriptional activities. Besides the well-known phosphorylation modifications on tyrosine and serine/threonine residues, recent studies have identified several other covalent modifications, such as ubiquitylation and sumoylation. These post-translational modifications of steroid receptors affect its stability, subcellular localization, and/or cofactor recruitment; eventually influence the duration and extent of transcriptional activation. This review is to focus on the recent research progress on the transcriptional activation of nuclear ER and PR as well as their physiological functions in early pregnancy, which may help us to better understand related female reproductive diseases.
Ligands ; Phosphorylation ; Receptors, Estrogen ; Receptors, Progesterone ; Sumoylation ; Transcriptional Activation

BACKGROUND: Long-term use of topical steroids for inflammatory skin diseases can induce complications, and efforts to find a better treatment are being continued. Peroxisome proliferator activated receptor alpha (PPARalpha) suppresses the skin's inflammatory reaction, maintains the homeostasis of the skin, and plays an important role in skin barrier function. OBJECTIVE: This study analyzed the effects of a skin moisturizer containing PPARalpha activator on various inflammatory skin diseases causing facial erythema and evaluated the observed improvements. METHODS: The PPARa activator used for this study is composed of supercritical extracts from Euryale ferox, Euphorbia lathyris, and Rosa multiflora, which showed significant effects in the transactivation assay compared to Wy14643. Moisturizer containing PPARalpha was applied to the faces of 31 patients with symmetric facial erythema, with PPARalpha applied on one-half of the face and a control moisturizer on the other half of the face twice a day for 2 weeks. The percentage of erythema index, erythema index, skin hydration, and transepidermal water loss was checked to evaluate treatment effect. Both patients and clinicians each assessed the improvement of erythema on both sides of a patient's face. RESULTS: Moisturizer containing PPARalpha agonist significantly improved erythema index measured with Mexameter MX18(R) and percentage of erythema index by polarization color imaging system (DermaVision-PRO(R)) (p<0.05). However, there was no significant improvement in skin hydration and transepidermal water loss. Improvement of erythema was also shown on both the patient and clinician graded assessments. CONCLUSION: Topical PPARalpha agonist applied during clinical practice was relatively safe and effective. This can be applied clinically to various inflammatory skin diseases causing erythema.
Erythema* ; Euphorbia ; Homeostasis ; Humans ; PPAR alpha* ; Rosa ; Skin ; Skin Diseases ; Steroids ; Transcriptional Activation

Kahweol as a coffee-specific diterpene has been reported to induce apoptosis in human cancer cells. Although some molecular targets for kahweol-mediated apoptosis have been elucidated, the further mechanism for apoptotic effect of kahweol is not known. Activating transcription factor 3 (ATF3) has been reported to be associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which kahweol stimulates ATF3 expression and apoptosis in human colorectal cancer cells. Kahweol increased apoptosis in human colorectal cancer cells. It also increased ATF3 expression through the transcriptional activity. The responsible cis-element for ATF3 transcriptional activation by kahweol was CREB located between −147 to −85 of ATF3 promoter. ATF3 overexpression increased kahweol-mediated cleaved PARP, while ATF3 knockdown attenuated the cleavage of PARP by kahweol. Inhibition of ERK1/2 and GSK3β blocked kahweol-mediated ATF3 expression. The results suggest that kahweol induces apoptosis through ATF3-mediated pathway in human colorectal cancer cells.
Activating Transcription Factor 3* ; Apoptosis* ; Coffee* ; Colorectal Neoplasms* ; Humans* ; Transcriptional Activation

Stored maternal factors in oocytes regulate oocyte differentiation into embryos during early embryonic development. Before zygotic gene activation (ZGA), these early embryos are mainly dependent on maternal factors for survival, such as macromolecules and subcellular organelles in oocytes. The genes encoding these essential maternal products are referred to as maternal effect genes (MEGs). MEGs accumulate maternal factors during oogenesis and enable ZGA, progression of early embryo development, and the initial establishment of embryonic cell lineages. Disruption of MEGs results in defective embryogenesis. Despite their important functions, only a few mammalian MEGs have been identified. In this review we summarize the roles of known MEGs in mouse fertility, with a particular emphasis on oocytes and early embryonic development. An increased knowledge of the working mechanism of MEGs could ultimately provide a means to regulate oocyte maturation and subsequent early embryonic development.
Animals ; Cell Lineage ; Embryonic Development* ; Embryonic Structures ; Female ; Fertility ; Mice* ; Oocytes ; Oogenesis ; Organelles ; Pregnancy ; Transcriptional Activation

BACKGROUND: Basal cell carcinoma (BCC) is the most prevalent cancer in the western world, showing a rapid increase in incidence. Activation of the Sonic hedgehog/Patched (PTCH) and is sisnalling pathway, due to PTCH inactivation, is a key event in sporadic and familial BCC development in humans and is associated with transcriptional activation of specific target genes, including GLI-1. Recently, PTCH inactivation by UV-specific mutation has been reported to develop BCC. OBJECTIVE: To evaluate the expression pattern of GLI-1 oncogene in BCC of sun-exposed and non-exposed areas of skin. METHOD: We examined 20 cases of BCC, and 4 cases of BCC occurring in sun-exposed and non-exposed areas, using an immunohistochemical method with paraffin-embedded sections. RESULTS: The results were as follows. 1. All cases of BCC showed a positive staining for GLI-1 protein. 2. In the staining pattern of GLI-1 protein, BCC in both sun-exposed and non-exposed areas showed diffuse staining throughout the tumor lobules. Moreover, the degree of staining was not found to be different between the BCC of sun-exposed and non-exposed areas. CONCLUSION: These results suggest that increased GLI-1 expression is important for BCC development. And multiple factors, including PTCH mutation due to UV irradiation, may affect GLI-1 expression.
Carcinoma, Basal Cell* ; Humans ; Incidence ; Oncogenes ; Skin ; Transcriptional Activation ; Western World

CCR3 is a chemokine receptor that mediates the accumulation of allergic inflammatory cells, including eosinophils and Th2 cells, at inflamed sites. The regulatory sequence of the CCR3 gene, contains two Runt-related transcription factor (RUNX) 1 sites and two PU.1 sites, in addition to a functional GATA site for transactivation of the CCR3 gene. In the present study, we examined the effects of the cis-acting elements of RUNX1 and PU.1 on transcription of the gene in EoL-1 eosinophilic cells and Jurkat T cells, both of which expressed functional surface CCR3 and these two transcription factors. Introduction of RUNX1 siRNA or PU.1 siRNA resulted in a modest decrease in CCR3 reporter activity in both cell types, compared with transfection of GATA-1 siRNA. Cotransfection of the two siRNAs led to inhibition in an additive manner. EMSA analysis showed that RUNX1, in particular, bound to its binding motifs. Mutagenesis analysis revealed that all point mutants lacking RUNX1- and PU.1-binding sites exhibited reduced reporter activities. These results suggest that RUNX1 and PU.1 participate in transcriptional regulation of the CCR3 gene.
Eosinophils ; Mutagenesis ; RNA, Small Interfering ; T-Lymphocytes ; Th2 Cells ; Transcription Factors ; Transcriptional Activation ; Transfection

Spatially and temporally programmed expression of the Hox genes along the antero-posterior (A-P) axis is essential for correct pattern formation during embryonic development. An accumulating body of evidence indicates the pivotal role of spatial chromatin organization for the coordination of gene regulation. Recently, chromosome conformation capture (3C) technique has been developed and opened a new way to study chromosomal interactions in the nucleus. In this study, we describe 3C method we applied in F9 embryonic teratocarcinoma cells and demonstrate that the chromosomal interactions at Hox loci are successfully detected. Interestingly, at Hoxc loci, the abundance of intrachromosomal interactions with neighboring fragments was drastically decreased when the genes are expressed. These results indicate the possibility of the dynamic pattern of chromosomal interaction in association with the transcriptional regulation of Hox genes.
Axis, Cervical Vertebra ; Chromatin ; Embryonic Development ; Female ; Gene Expression ; Genes, Homeobox ; Pregnancy ; Teratocarcinoma ; Transcriptional Activation

OBJECTIVETo construct a subtractive cDNA library of genes transactivated by hepatitis B virus X protein (HBX) using suppression subtractive hybridization (SSH) technique and to clone genes associated with HBX transactivating function.

METHODSThe mRNA was isolated from HepG2 cells transfected with pcDNA3.1(-)-X and pcDNA3.1(-) empty vector respectively, then cDNA was synthesized. After restriction enzyme RsaI digestion, a number of small size cDNA was obtained. Then tester cDNA was subdivided into two portions and each was ligated with different cDNA adaptor. After tester cDNA was hybridized with driver cDNA twice and underwent nested polymerase chain reaction (PCR) twice the production was subcloned into T/A plasmid vectors to set up the subtractive cDNA library. Amplification of the library was carried out with E. coli strain JM109, some cDNA was sequenced and analyzed in GenBank with Blast.

RESULTSThe subtractive cDNA library of genes transactivated by HBX was constructed. The amplified library contained 85 positive clones, and colony PCR showed that these clones contained 200-1000 bp inserts. 65 clones were analyzed by sequencing and bioinformatics, which suggested nineteen known genes and fifteen genes with unknown function.

CONCLUSIONA subtractive cDNA library of genes transactivated by HBX using SSH technique has been constructed successfully, which may bring some new clues for studying the biological functions of HBX and the pathogenesis of hepatoma.

Cloning, Molecular ; Gene Library ; RNA, Messenger ; analysis ; Trans-Activators ; physiology ; Transcriptional Activation

Zinc-finger proteins have been widely studied due to their highly conserved structures and DNA-binding specificity of zinc-finger domains. However, researches on the zinc-finger proteins from microorganisms, especially those from prokaryotes, are still very limited. This review focuses on the latest progress on microbial zinc-finger proteins, especially those from prokaryotes and the application of artificial zinc-finger proteins in the breeding of robust strains. Artificial zinc-finger proteins with transcriptional activation or repression domain can regulate the global gene transcription of microbial cells to acquire improved phenotypes, such as stress tolerance to heat, ethanol, butanol, and osmotic pressure. Using the zinc-finger domain as DNA scaffold in the construction of enzymatic system can enhance the catalytic efficiency and subsequently the production of specific metabolites. Currently, zinc-finger domains used in the construction of artificial transcription factor are usually isolated from mammalian cells. In the near future, novel transcription factors can be designed for strain development based on the natural zinc-finger domains from different microbes, which may be used to regulate the global gene expression of microbial cells more efficiently.
Bacteria ; metabolism ; DNA ; chemistry ; Protein Engineering ; Transcription Factors ; chemistry ; Transcriptional Activation ; Zinc Fingers

OBJECTIVETo investigate the expression of microRNA-107 (miR-107) and its functional role in hepatocellular carcinoma(HCC).

METHODSThe gene chip data of HCC obtained from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database were used to analyze the expression levels of miR-107 in liver cancer. Twenty-two pairs of fresh surgical specimens of HCC and adjacent tissues and 53 paraffin-embedded specimens of HCC were examined for miR-107 expression by qRT-PCR. The correlation of the expression levels of miR-107 with the clinicopathologic characteristics of the patients were analyzed. The role of miR-107 in regulating the proliferation of hepatocellular carcinoma cells were determined by MTT assay in Huh7 cells transfected with a miR-107 mimic or inhibitor.

RESULTSThe expression levels of miR-107 were significantly up-regulated in HCC tissues as compared to the adjacent tissues (P<0.05) in positive correlation with the tumor size (P<0.032). Transfection with miR-107 mimics significantly promoted the cell proliferation (P<0.0001) while miR-107 inhibitor inhibited the cell proliferation (P<0.0001).

CONCLUSIONThe expression of miR-107 is up- regulated in HCC tissues and its expression levels are correlated with HCC cell proliferation, suggesting its role as a potential oncogene in liver cancer.

Carcinoma, Hepatocellular ; genetics ; Cell Proliferation ; Humans ; Liver Neoplasms ; genetics ; MicroRNAs ; genetics ; Transcriptional Activation ; Up-Regulation