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

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

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

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

Autopsy ; Brain ; metabolism ; pathology ; Gene Expression ; physiology ; Humans ; Transcriptional Activation ; physiology

The purpose of this study was to characterize the genetic contribution to endothelial adaptation to exercise training. Vasoreactivity was assessed in aortas from four inbred mouse strains (129S1, B6, NON, and SJL) after 4 weeks of moderate intensity continuous exercise training (MOD), high intensity interval training (HIT) or in sedentary controls (SED). Intrinsic variations in endothelium-dependent vasorelaxation (EDR) to acetylcholine (ACh) as well as vasocontractile responses were observed across SED groups. For responses to exercise training, there was a significant interaction between mouse strain and training intensity on EDR. Exercise training had no effect on EDR in aortas from 129S1 and B6 mice. In NON, EDR was improved in aortas from MOD and HIT compared with respective SED, accompanied by diminished responses to PE in those groups. Interestingly, EDR was impaired in aorta from SJL HIT compared with SED. The transcriptional activation of endothelial genes was also influenced by the interaction between mouse strain and training intensity. The number of genes altered by HIT was greater than MOD, and there was little overlap between genes altered by HIT and MOD. HIT was associated with gene pathways for inflammatory responses. NON MOD genes showed enrichment for vessel growth pathways. These findings indicate that exercise training has non-uniform effects on endothelial function and transcriptional activation of endothelial genes depending on the interaction between genetic background and training intensity.
Acetylcholine ; Animals ; Aorta ; Endothelium ; Gene Expression Profiling ; Genetic Background ; Mice ; Mice, Inbred Strains ; Transcriptional Activation ; Vasodilation

Human bocavirus 1 (HBoV1) non-structural protein NS1 is a multifunctional protein important for virus replication and induction of apoptosis in host cell. To better understand the function of the NS1 protein, it is urgent to address reducing the toxicity of NS1 to host cells. In the present study, we established a stable cell line that regulates expression of NS1 of HBoV1. The recombinant lentivirus plasmid containing a regulatable promoter fused with ns1 gene was constructed and transfected into HEK 293T cells using transfection reagent. The HEK 293T cell lines stably expressing NS1-100 and NS1-70 proteins were established by screening resistant cells with puromycin and inducing NS1 expression with doxycycline. The expression of NS1 protein was determined by fluorescent labeling protein and Western blotting. HBoV1 promoter was transfected into stably expressing NS1 cell line and its trans-transcriptional activity was analyzed. The results showed that NS1 protein was expressed stably in the established cell lines and had a strong activation activity on the HBoV1 promoter driving luciferase gene. Taken together, this study provides a solid basis for further research on the function of NS1 and the pathogenesis of human bocavirus.
Human bocavirus ; Promoter Regions, Genetic ; Transcriptional Activation ; Viral Nonstructural Proteins ; Virus Replication