These intriguing results were confirmed in a diet-induced obesity and insulin resistance model. Liver-specific knockout of Lrh-1 had no effect on development of obesity and diabetes

when a high-fat diet was applied over 15 weeks. However, DLPC treatment substantially improved Bortezomib glucose homeostasis, and decreased hepatic glucose production, and serum glucose and insulin levels. Improved hepatic insulin sensitivity may have been caused by increased insulin-dependent phosphorylation of the insulin receptor IRS2. Despite unchanged food intake, total body weight, and liver weight, hepatic triglycerides and NEFAs were reduced following DLPC administration and mouse livers showed reduced steatosis. Mechanistically, DLPC markedly decreased expression of genes associated with de novo lipogenesis, especially the lipogenic transcription factor Srebp-1c and its key downstream targets Acc-2, Scd-1, and Fasn. However, no effects of DLPC were observed on hepatic expression of a number of genes controlling glucose homeostasis. It is noteworthy that both serum and hepatic bile salts nearly doubled following DLPC treatment, alongside an induction of Cyp7a1 and Cyp8b1 in the liver. All reported effects of DLPC

were absent when LRH-1 was conditionally deleted in the liver. DLPC thus proved to be of potential find more therapeutic benefit in both genetic and diet-induced models of insulin resistance. Encouraged by these results, Lee et al. suggest that DLPC might be a promising therapeutic agent for the treatment of metabolic medchemexpress disorders. Consequently, the group has initiated a clinical trial to explore the effect of DLPC in prediabetic

patients. How does DLPC improve insulin sensitivity and reduce steatosis? The authors reason that the beneficial effect of DLPC on steatosis might be a result of the markedly decreased expression of Srebp-1c and/or decreased insulin levels. They propose the following regulatory loop (Fig. 1): Lrh-1-dependent repression of Srebp-1c expression may improve steatosis, increase insulin sensitivity, and hence decrease serum insulin; and decreased insulin levels in turn may reinforce repression of Srebp-1c,5 further ameliorating steatosis. This model is supported by previous data from other groups: the repression of Srebp-1c by way of Lrh-1 is consistent with a functional antagonism of SREBP-1c transactivation by LRH-16 and Srebp-1c target genes Acc-2 and Scd-1 have been shown to modulate β-oxidation, hepatic steatosis, and insulin resistance.1 Do bile salts contribute to the antidiabetic and antisteatotic effects of DLPC? Upon DLPC treatment, bile salts in serum and more strikingly in liver tissue were markedly increased. This is remarkable because hepatic bile salt levels are tightly controlled. Feeding a 1% cholate (w/w) diet only induces an increase of hepatic bile salts by approximately 50% in mice.

For example, the horns of ceratopsians might satisfy all four (five) criteria listed above for both MRH and SRH, but would not pass the test of high sexual dimorphism required for sexual selection; on the other hand, they appear to pass the two tests of the species recognition hypothesis (non-directional variation of bizarre structures and several sympatric species). Moreover, without a clear demonstration of sexual dimorphism, the MRH reduces to the social

selection hypothesis (Hieronymus et al., 2009). Our purpose is not to insist that species recognition has been the only cause of the evolution of bizarre structures in dinosaurs, nor that adaptation, social selection and sexual selection have been unimportant in dinosaurian evolution. We merely ask in each case: how would we test this? We conclude that the hypotheses of mechanical function and sexual display that have predominated for decades as general explanations check details of the evolution selleck screening library of these structures in dinosaurian clades are unfounded. When we test the hypothesis that presumed functions of these structures have evolved in their clades, we find no evidence; hence the notions that these structures are ‘adaptations’ fail the criteria proposed by evolutionary biologists (Greene, 1986; Williams, 1992; Rose & Lauder, 1996; Padian, 2001). Furthermore,

sexual dimorphism has not been strongly established for any bizarre structures in dinosaurian lineages, even though mild dimorphism has been statistically demonstrated in at least one lineage and may be plausible in others.

If criteria of sexual behavior other than those based on sexual selection (which requires sexual MCE公司 dimorphism: Darwin (1871) are to be proposed, they should be justified on grounds that are more stringent than weak analogies to very different living organisms. We stress that no evolutionary hypothesis can be regarded as a ‘default’ explanation (i.e. if a certain class of explanation fails, then another one is automatically strengthened or must be accepted by default). Hypotheses must be independently tested, or they are not scientific. In many or most cases, definitive tests will not be possible. We have proposed two tests of a Species Recognition hypothesis, and there may be others. In our view, most dinosaurian bizarre structures pass these tests, but they do not pass the tests of adaptation or of sexual display. The importance of social selection (Hieronymus et al., 2009) remains to be tested in dinosaurs beyond individual species. This does not mean that these structures were not adaptive or used in attracting mates; we simply have no evidence on these points at present. Our hypothesis is that the Species Recognition Hypothesis is simpler and more general in explaining the evolution of bizarre structures in dinosaurs than those of mechanical function, social selection, or sexual selection/mate recognition.

Disclosures: The following people have nothing to disclose: Bonnie A. Ewald, Alysse G. Wurcel, Sonali Paul, Kathleen Viveiros BACKGROUND: Subsaharan Africa (SSA) has one of the highest global rates of HCV infection, accounting for nearly 20% of all global cases. However, little is known about the population level epidemiology, including the predominant risk factors for transmission. Such information is necessary to help guide screening and management guidelines, especially with the increasing availability of effective anti-virals. METHODS: We conducted

a case-control study of prior blood donors at Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana to identify risk factors and potential transmission mechanisms of HCV. KATH is a tertiary referral Selleckchem AZD1208 hospital, receiving patients from across Ghana. A series of 180 consecutive cases that tested positive with the HCV rapid screen assay (RSA) were matched to 183 negative donors. New blood samples were taken to confirm HCV infection, assess for co-infections and an extensive survey administered to identify risk factors for infection. HCV testing including HCV Antibody confirmation, HCV quantitative viral load testing, as well as HBV and HIV serologic assessment. RESULTS: 87 individuals were identified as true infections after repeat serologic evaluation. There was no difference see more in age and gender between infected

and non-infected individuals. HCV infected individuals were more often born at home, have tribal scarring, and circumcision MCE outside of a clinic or hospital setting. There was also a significant association with HBV co-infection, but not HIV infection. Of importance, the most highly significant association was with region of tribal origin; individuals from the upper and northern regions of Ghana were 18.9 (8.4-42.6;p<0.001) and 6.6 (2.4-18.2;p<0.001) more likely to be infected with HCV, compared to individuals from other regions

in Ghana. CONCLUSIONS: These data suggest that several transmission modes, particularly those associated with cultural skin-piercing practices, are likely to be contributing to the current HCV epidemic in Ghana, West Africa, and the distribution of these cultural practices may have led to substantial regional variation in HCV prevalence. Disclosures: The following people have nothing to disclose: Jennifer E. Layden, Richard O. Phillips, Fred S. Sarfo, Dorcas O. Owusu, Nallely Mora, Joseph Forbi, Stephanie Kliethermes, Shirley P. Owusu-Ofori, Ohene Opare-Sem, Kenrad Nelson, Richard Cooper Background HIV/HCV co-infection is very common in the South China mainly caused by intravenous drug using, and poor sustained virological response (SVR) had also been found in HIV/HCV co-infection with the therapy of Interferon plus Rib-avirin in South China.

Disclosures: The following people have nothing to disclose: Bonnie A. Ewald, Alysse G. Wurcel, Sonali Paul, Kathleen Viveiros BACKGROUND: Subsaharan Africa (SSA) has one of the highest global rates of HCV infection, accounting for nearly 20% of all global cases. However, little is known about the population level epidemiology, including the predominant risk factors for transmission. Such information is necessary to help guide screening and management guidelines, especially with the increasing availability of effective anti-virals. METHODS: We conducted

a case-control study of prior blood donors at Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana to identify risk factors and potential transmission mechanisms of HCV. KATH is a tertiary referral selleck chemical hospital, receiving patients from across Ghana. A series of 180 consecutive cases that tested positive with the HCV rapid screen assay (RSA) were matched to 183 negative donors. New blood samples were taken to confirm HCV infection, assess for co-infections and an extensive survey administered to identify risk factors for infection. HCV testing including HCV Antibody confirmation, HCV quantitative viral load testing, as well as HBV and HIV serologic assessment. RESULTS: 87 individuals were identified as true infections after repeat serologic evaluation. There was no difference CHIR-99021 in vivo in age and gender between infected

and non-infected individuals. HCV infected individuals were more often born at home, have tribal scarring, and circumcision 上海皓元 outside of a clinic or hospital setting. There was also a significant association with HBV co-infection, but not HIV infection. Of importance, the most highly significant association was with region of tribal origin; individuals from the upper and northern regions of Ghana were 18.9 (8.4-42.6;p<0.001) and 6.6 (2.4-18.2;p<0.001) more likely to be infected with HCV, compared to individuals from other regions

in Ghana. CONCLUSIONS: These data suggest that several transmission modes, particularly those associated with cultural skin-piercing practices, are likely to be contributing to the current HCV epidemic in Ghana, West Africa, and the distribution of these cultural practices may have led to substantial regional variation in HCV prevalence. Disclosures: The following people have nothing to disclose: Jennifer E. Layden, Richard O. Phillips, Fred S. Sarfo, Dorcas O. Owusu, Nallely Mora, Joseph Forbi, Stephanie Kliethermes, Shirley P. Owusu-Ofori, Ohene Opare-Sem, Kenrad Nelson, Richard Cooper Background HIV/HCV co-infection is very common in the South China mainly caused by intravenous drug using, and poor sustained virological response (SVR) had also been found in HIV/HCV co-infection with the therapy of Interferon plus Rib-avirin in South China.

Altogether, our data show a significant association between poor treatment-response associated alleles of IL28B and slow FPR in genotype non-1 infected

patients. Our data also show an association between the poor treatment-response associated allele of IL28B and decreased necroinflammatory activity among patients with non-1 genotypes. In genotype 1 patients, a similar association was detected, but only when using the recessive Lumacaftor ic50 mode of inheritance. This is consistent with the Japanese study, in which the association with rs8099917 was significant when using the recessive mode of inheritance.29 The IDEAL study showed an association between the poor treatment response allele of another marker (i.e., rs12979860) and lower necroinflammatory activity in genotype-1 infected patients, when using the dominant mode of inheritance.30 Differences in the significance of the association may be explained by the use of different study designs (treatment-oriented clinical trial versus cohort study) and sample sizes. Differences in the significance level of rs8099917 and rs12979860 with regard to viral clearance were also reported among studies. Both polymorphisms may be in linkage disequilibrium with another or several other polymorphism(s) with a functional effect. Until such polymorphism(s) has/have been identified,

it is difficult to speculate why rs8099917 or rs12979860 may provide stronger associations with any of the above phenotypes. These differences probably result from differences in the statistical power (due to http://www.selleckchem.com/products/LDE225(NVP-LDE225).html different allele frequencies) and/or the degree

of linkage disequilibrium that each SNP has with the functional polymorphism(s). Notwithstanding these apparent discrepancies, these studies establish a link between the poor treatment-response alleles of IL28B and lower necroinflammatory activity. Regarding FPR, MCE公司 our study suggests that this association is stronger in patients infected with HCV non-1 genotypes than in those infected with genotype 1. These data add to the factors influencing FPR in chronic hepatitis C, and may be useful to implement targeted therapeutic interventions in patients at risk of rapid liver disease progression. Elevated ALT levels tended to be less frequent among patients carrying the minor alleles of IL28B, but the association did not reach significance. In contrast, data from the IDEAL study showed a significant association between these alleles and lower ALT levels in genotype 1-infected patients.30 Necroinflammatory activity and/or elevated ALT levels have sometimes been associated with a good treatment response,33-35 including in the IDEAL study.36 However, necroinflammatory activity is not universally considered a favorable predictor of virological response to therapy of chronic hepatitis C,18 although there is evidence that a strong HCV-specific CD8+ response predicts both a fast viral decline during therapy and SVR.

7 versus WM: 2,775 ± 492.5, n = 5, P < 0.05; and Fig. 4C, liver histology). To confirm that Gsk3β inactivation functioned downstream of PI3 kinase activation, SB216763 and wortmannin were administered in concert prior to the ischemia insult. Gsk3 inhibition remained hepatocytoprotective against IRI in the presence of PI3 kinase inhibition (Fig. 4D, sALT: Ctl, 7,825 ± 583.9 versus SB, 3,511 ± 809.0; P < 0.01; WM, 8,863 ± 826.9 versus SB/WM, 3,069 ± 741.7; P < 0.01). Thus, PI3 kinase-dependent Gsk3β phosphorylation serves as a self-regulatory mechanism of liver homeostasis

to limit the excessive IR-triggered tissue damage. It has been well established that TLR4 activation is the key step in liver inflammatory immune response against IR.5, 9 To investigate the cellular mechanism of our in vivo findings, we analyzed the effects of Gsk3 inhibition in macrophage Pembrolizumab response to TLR4 stimulation in vitro. Bone marrow-derived macrophages were stimulated with LPS in the absence or presence of SB216763. As shown in Fig. 5A, Gsk3 inhibition significantly reduced IL-12p40 and IL-1β, but increased IL-10 gene induction

at 1 hour of culture. In contrast, the induction of TNF-α, IL-6, and CXCL10 were unaffected at this early timepoint. By 6 hours, whereas Buparlisib manufacturer the IL-12p40 expression remained lower, levels of TNF-α, IL-6, IL-1β, and CXCL10 all became significantly reduced. IL-10 levels were comparable between the two groups. Gsk3 inhibition did not alter LPS-induced MAP kinase activation, as the phosphorylation kinetics of JNK, Erk, and p38 were similar in control and SB-treated macrophage cultures (Fig. 5B). The disparities between IL-12/IL-10 and TNF-α/CXCL10 genes at the timepoints

regulated by the Gsk3 inhibition indicated a possible difference in their regulatory mechanisms, i.e., the early regulated genes were the primary targets of Gsk3, whereas the later ones were regulated by the primary gene products. To test whether IL-10 may represent such a primary gene regulating the late inhibition of TNF-α/CXCL10 induction, we added anti-IL-10 Ab in SB216763-treated macrophage cultures. medchemexpress Indeed, LPS-induced TNF-α/CXCL10 levels at 6 hours, which remained diminished by Gsk3 inhibitor alone, became restored (or even enhanced) after adjunctive anti-IL-10 Ab and SB216763 (Fig. 5C). Interestingly, anti-IL-10 Ab restored otherwise suppressed IL-12p40 gene induction by SB216763. Thus, Gsk3 inhibition regulates macrophage TLR4 response by directly down-regulating the pro-inflammatory IL-12 gene, yet up-regulating the induction of immune regulatory IL-10, which, in turn, further suppresses the pro-inflammatory gene expression programs. Although Gsk3β has been shown to regulate macrophage cytokine production and hepatocyte apoptosis,12, 21 its role in liver IRI cascade, an inflammation-mediated hepatocellular injury process, has not been explored.

4A). In line with the decrease in Srebp1c Staurosporine solubility dmso mRNA levels in mice challenged with TM, the nucleic mature Srebp1c protein expression was also diminished. Both WT and ATGL KO mice challenged with TM showed low mRNA levels for Cpt1α (Fig. 4B), whereas acyl CoA oxidase mRNA levels were not changed in mice challenged with TM (data not shown). Moreover, Acc2 expression (responsible for malonyl-CoA generation potentially inhibiting Cpt1α) was similarly repressed in WT and ATGL KO mice after TM injection. These findings demonstrate that de novo

lipogenesis and FA β-oxidation cannot explain the differences in hepatic lipid accumulation and ER stress. Next, we explored gene-expression levels of key players involved in hepatic TG synthesis: acylglycerol-3-phosphate O-acyltransferase 9 (Agpat9; also known as Gpat3) and acylglycerol-3-phosphate O-acyltransferase 3 (Agpat3; also known as Lpaat). mRNA expression levels of these genes (Fig. 5) were not increased in WT mice upon TM treatment, whereas TM-treated ATGL KO mice showed a marked increase in the expression of Agpat9 (Gpat3) (8-fold) and Agpat3 (Lpaat) (2.5-fold), compared to untreated ATGL KO mice. Collectively, these findings suggest that an increase in hepatic TG formation in ATGL KO mice

challenged with TM may be involved in protection against the induction of ER stress. Because TM-injected mice exhibited selective fat accumulation in ATGL KO (but not WT) livers, we next addressed click here the effect of TM treatment on serum and hepatic FA species and their potential role in ER stress induction or protection by measuring free serum as well as total and free hepatic FA composition in nonfasted mice (Supporting Fig. 6; Fig. 6A; Supporting Table 1). Interestingly, TM treatment resulted in an increase of total hepatic PA (16:0) and OA (18:1n9) levels in both WT and ATGL KO mice. However, only untreated WT mice showed 上海皓元医药股份有限公司 higher amounts of total PA related to OA at the baseline (Fig. 6B). In contrast, ATGL KO mice exhibited higher levels of OA before and

after TM injection, reflected by a lower PA/OA ratio (as shown in Fig. 6B). In line with the changes in PA/OA ratios, Scd1-the enzyme responsible for FA desaturation-was down-regulated under TM treatment (Fig. 6C), indicating that TM-treated WT mice are not able to convert potentially lipotoxic PA into nontoxic-or even protective-OA; in contrast, ATGL KO mice exposed to TM might have been protected by their higher basal amount of OA from PA-induced ER stress. In line with our hypothesis, phosphoinositide-3-kinase inhibitor 1 (Pik3ip1) mRNA was up-regulated in WT, but not in ATGL KO, mice subjected to TM (Fig. 6D). Pik3ip1 expression is induced by PA in vitro34 and plays an essential role in PA-induced ER stress.

grandifolius must have released (a) molecule(s) that can be oxidized by catalase either into a strong oxidant itself or with concomitant superoxide production. There is only one known

instance of a catalase-activated oxidant mediating a biological relationship, and that involves the synthetic frontline tuberculosis drug isoniazid, or isonicotinic acid hydrazide (INH). INH reacts with the Mycobacterium tuberculosis catalase-peroxidase KatG to form a highly reactive radical that interferes in the essential mycolic acid pathway IWR 1 (reviewed in Vilcheze and Jacobs 2007). The M. tuberculosis KatG is a dimeric bifunctional catalase-peroxidase, while bovine liver catalase is a tetrameric monofunctional clade 3 catalase. Clade 3 catalases originated in a single bacterial taxon and spread to other prokaryotes and eukaryotes by lateral gene transfer (Klotz and Loewen 2003). As a result, bacterial clade 3 catalases are very similar in sequence and structure to bovine liver catalase.

It is possible that the bovine liver catalase-activated oxidant observed in wounded H. grandifolius is a defense against a marine bacterial pathogen containing a clade 3 catalase. Since wounding is an essential component of grazing, we examined Dabrafenib chemical structure the oxidant response to grazing in P. decipiens. After exposure to amphipod grazers for several hours, grazed P. decipiens tissue produced significantly more strong oxidants than neighboring, ungrazed tissue. ROS play an established role in macroalgal microbial defense (Weinberger 2007), and they are likely important for protection against infection after grazing. In addition, although ROS production in macroalgae has not been tested as a defense against marine grazers, here we show that it is possible. Marine meso- and micro-grazers are small and often live on the plants that they eat. The creation of an oxidizing microhabitat

by the diffusion of strong oxidants from a graze wound might affect grazer fitness by modifying medchemexpress feeding, health, or reproduction. The Antarctic macroalgae surveyed showed diversity in their oxidative responses to wounding. We studied in detail three brown algae; two in the same family (D. anceps and H. grandifolius; Desmarestiaceae) and one comprising its own order (A. mirabilis; Ascoseirales), and two reds from different orders (P. decipiens and T. antarcticus; Palmeriales and Gigartinales, respectively). There is no a priori reason to expect the oxidative response to be strikingly similar, considering the length of time since evolutionary divergence (Keeling et al. 2005). The fact that an oxidative response to wounding has been conserved among Antarctic macroalgae along with plants and animals lends support for an important and ancient role of oxidants in healing and/or defense.

grandifolius must have released (a) molecule(s) that can be oxidized by catalase either into a strong oxidant itself or with concomitant superoxide production. There is only one known

instance of a catalase-activated oxidant mediating a biological relationship, and that involves the synthetic frontline tuberculosis drug isoniazid, or isonicotinic acid hydrazide (INH). INH reacts with the Mycobacterium tuberculosis catalase-peroxidase KatG to form a highly reactive radical that interferes in the essential mycolic acid pathway Hydroxychloroquine mw (reviewed in Vilcheze and Jacobs 2007). The M. tuberculosis KatG is a dimeric bifunctional catalase-peroxidase, while bovine liver catalase is a tetrameric monofunctional clade 3 catalase. Clade 3 catalases originated in a single bacterial taxon and spread to other prokaryotes and eukaryotes by lateral gene transfer (Klotz and Loewen 2003). As a result, bacterial clade 3 catalases are very similar in sequence and structure to bovine liver catalase.

It is possible that the bovine liver catalase-activated oxidant observed in wounded H. grandifolius is a defense against a marine bacterial pathogen containing a clade 3 catalase. Since wounding is an essential component of grazing, we examined EPZ-6438 price the oxidant response to grazing in P. decipiens. After exposure to amphipod grazers for several hours, grazed P. decipiens tissue produced significantly more strong oxidants than neighboring, ungrazed tissue. ROS play an established role in macroalgal microbial defense (Weinberger 2007), and they are likely important for protection against infection after grazing. In addition, although ROS production in macroalgae has not been tested as a defense against marine grazers, here we show that it is possible. Marine meso- and micro-grazers are small and often live on the plants that they eat. The creation of an oxidizing microhabitat

by the diffusion of strong oxidants from a graze wound might affect grazer fitness by modifying MCE feeding, health, or reproduction. The Antarctic macroalgae surveyed showed diversity in their oxidative responses to wounding. We studied in detail three brown algae; two in the same family (D. anceps and H. grandifolius; Desmarestiaceae) and one comprising its own order (A. mirabilis; Ascoseirales), and two reds from different orders (P. decipiens and T. antarcticus; Palmeriales and Gigartinales, respectively). There is no a priori reason to expect the oxidative response to be strikingly similar, considering the length of time since evolutionary divergence (Keeling et al. 2005). The fact that an oxidative response to wounding has been conserved among Antarctic macroalgae along with plants and animals lends support for an important and ancient role of oxidants in healing and/or defense.

4F). The results suggest

that ZNF191 may act as a mediator of serum induction of β-catenin mRNA expression in HCC cells. It is clear that ZNF191 can positively regulate mRNA and protein levels of β-catenin. Next we sought to determine the mechanism of this regulation. To this end we assessed whether overexpression of ZNF191 has any effect on transcription activity of the CTNNB1 promoter. Promoter luciferase assay indicated that ZNF191 can increase the transcription activity of the full-length CTNNB1 promoter (PGL3-HBCP, gift of Prof. R.H. Dashwood, Oregon State University) by about 3.5-fold compared with transfecting control vector (Fig. 5A). Furthermore, this activation was in a dose-dependent manner (Fig. 5B). Compared with the full-length isoform of ZNF191 (ZNF191-FU), the short isoform of ZNF191 (ZNF191-NF, without C2H2 zinc finger domain) had no activation effect on CTNNB1 Selleck MAPK Inhibitor Library promoter (Fig. 5B). This result suggests that ZNF191 exerts this activation function role by way of C2H2

zinc finger domain. Because cyclin D1 is the downstream gene of β-catenin, we assessed the effect of ZNF191 on CCND1 promoter. Figure 5C shows that ZNF191 increased CCND1 promoter by 6.4-fold. Mutation in the LEF/TCF site (the binding site of β-catenin) of the CCND1 promoter resulted in a much lower increase (3.2-fold) in transcription activity. In vivo ChIP assays showed that ZNF191 cannot directly bind to the CCND1 promoter (-962CD1), including the LEF/TCF site of the CCND1 promoter (Supporting Fig. 4). The results suggest that activation of CCND1 promoter by ZNF191 is through β-catenin, but not through direct binding of endogenous ZNF191 to the promoter. selleck Next, in order to identify ZNF191 response regions in the CTNNB1 promoter, various lengths of CTNNB1 5′-flanking region (Fig. 5D) were transfected into HEK-293T cells with pCMV-Myc-ZNF191 to determine the promoter transcriptional activities.

The luciferase reporter assay indicated that the construct P(-1407/+93) exhibited the maximum luciferase activity, which was much higher than that of P(-2692/+93) and P(-1907/+93). P(-907/+93) and P(-409/+93) constructs displayed modest promoter activity (Fig. 4E). These results suggest that nucleotide (nt)-1407/-907 of the CTNNB1 promoter region is 上海皓元 indispensable to elicit transcriptional response for ZNF191. The finding that potential binding sites for ZNF191 are located at nt-1407/-907 of CTNNB1 promoter region prompted us to determine whether ZNF191 is directly binding to the CTNNB1 promoter. With delicate analysis of the nucleotide sequences of the 5′-flanking region (-1467/-907) of the β-catenin gene (Fig. 6A, top), we found that sequences ATTAATT at nt-1244 of the CTNNB1 promoter are similar to ATTCATT (within three repetitions of [TCAT] motif, TCATTCATTCAT, defined previously as ZNF191 interacting motif21). We hypothesized that ZNF191 may directly bind to the CTNNB1 promoter at this candidate site (Fig. 6A).