ライフサイエンスコーパス: TCF7L2

1 romoter of the increased target genes (i.e., TCF7L2).

2 d in parvocellular and koniocellular layers (TCF7L2).

3 , and beta2 (ADRB2) and transcription factor TCF7L2.

4 ibility in conjunction with gene variants in TCF7L2.

5 nriched in the sites bound by both GATA3 and TCF7L2.

6 -specific pattern of alternative splicing of TCF7L2.

7 gate mechanisms of target gene regulation by TCF7L2.

8 cence staining and coimmunoprecipitated with Tcf7l2, a canonical Wnt signaling transcription factor.

9 Polymorphism in TCF7L2, a component of the canonical Wnt signaling pathw

10 ymmetry, we identified two mutant alleles of tcf7l2, a gene that encodes a transcriptional regulator

11 ved intronic region within the gene encoding Tcf7l2, a key mediator of canonical Wnt signaling.

12 e that the MUC1-C oncoprotein contributes to TCF7L2 activation and thereby promotes cyclin D1 express

13 potential mechanism through which pericytic Tcf7l2 activity affects beta-cells.

14 Here, we show that Tcf7l2 activity in pancreatic pericytes is required for

15 al cellular mechanism through which abnormal TCF7L2 activity predisposes individuals to diabetes and

16 Tcf7l2 acts cell automously in nascent equipotential neu

17 However, the mechanisms by which TCF7L2 affect insulin secretion are still unclear.

18 ith opposing effects (eg, the same rs7901695/TCF7L2 allele is associated with increased odds of high

19 We show that a null Tcf7l2 allele leads, in a dose-dependent manner, to lowe

20 iabetes incidence in carriers of the at-risk TCF7L2 alleles.

21 Transcription factor 7-like 2 (TCF7l2), also known as TCF4, is a Wnt effector induced t

22 loss on transcription factor 7-like 2 gene (TCF7L2) alternative splicing in adipose tissue and liver

23 Variants near TCF7L2 and ADRA2A were associated with reduced glucose-i

24 Our GWAS identified two known loci (TCF7L2 and KCNQ1) reaching genome-wide significance leve

25 also downregulated the transcription factor TCF7L2 and markedly reduced WNT signaling.

26 TCF7L2 and MUC1-C form a complex on the cyclin D1 gene p

27 ISL1 is a primary target of TCF7L2 and regulates proinsulin production and processin

28 UC1-C inhibitor blocked the interaction with TCF7L2 and suppressed cyclin D1 levels.

29 Two of these loci map to genes (TCF7L2 and TGFB1) with established roles in colorectal t

30 MUC1-C blocks the interaction between TCF7L2 and the C-terminal-binding protein (CtBP), a supp

31 heterozygous for null alleles of Cacna1c and Tcf7l2 and wild-type females from 30 inbred laboratory s

32 We conclude that TCF7L2 and Wnt signaling control gut and brain gcg expre

33 ween variants rs1799884 (GCK) and rs7903146 (TCF7L2) and OGTT outcomes at 24-32 weeks' gestation in 3

34 entially bind transcription factor 7-like 2 (TCF7L2) and that the risk region physically interacts wi

35 1 gene (rs4689388 and rs1801214), rs7903146 (TCF7L2), and 3 SNPs in the KCNQ1 gene (rs231362, rs22378

36 loci with known islet function, e.g., PDX1, TCF7L2, and ADCY5 Importantly, binding sites previously

37 nal evidence of pleiotropy for APOE, TOMM40, TCF7L2, and CETP variants, many with opposing effects (e

38 -onset type 1 diabetes loci and FCRL3, GAD2, TCF7L2, and FTO.

39 esenting 7,046 genes including PPARG, KCNQ1, TCF7L2, and IRS1, showed differential DNA methylation in

40 trate a novel relationship between GATA3 and TCF7L2, and reveal important insights into TCF7L2-mediat

41 between SNPs, with the exception of those in TCF7L2, and type 2 diabetes in African Americans.

42 3, ENPP1, FTO, LEP, PPARG, PPARGC1A, SLC2A2, TCF7L2, and UCP2) associated with type 2 diabetes or obe

43 rphism in Wnt-regulated transcription factor TCF7L2 are associated with dysregulation of glucose meta

44 Common genetic variants in GCK and TCF7L2 are associated with higher fasting glucose and ty

45 The discovery of TCF7L2 as a global type 2 diabetes (T2D) gene has sparke

46 udes the transcription factor 7-like 2 gene (TCF7L2), as well as other type 2 diabetes mellitus-assoc

47 type 2 diabetic subgroup, and for rs7903146 (TCF7L2), association was observed for early-onset type 2

48 beta-catenin, transcription factor 7-like 2 (TCF7L2), attenuated insulin secretion, consistent with t

49 of 149 DEGs was suggested by strong proximal TCF7L2 binding (peak proximity score > 10) and early mRN

50 nformatic analysis of the cell type-specific TCF7L2 binding sites revealed enrichment for multiple tr

51 We identified 116,000 non-redundant TCF7L2 binding sites, with only 1,864 sites common to th

52 depleted GATA3 in MCF7 cells and showed that TCF7L2 binding was lost at a subset of sites.

53 only synthesis of proinsulin is regulated by TCF7L2 but also processing and possibly clearance of pro

54 etabolic effect of a functional knockdown of TCF7L2 by generating transgenic mice that express domina

55 asmic domain (MUC1-CD) binds directly to the TCF7L2 C-terminal region.

56 in 7 genes (APOA1, IL1alpha, IL1beta, TLR4, TCF7L2, CCK1Rec, and STAT3) after correction for phenoty

57 iobank participants, we observed three (near TCF7L2, CDKN2AB and CDKAL1) overestimated (body mass ind

58 recurrent mutations in the Wnt pathway gene TCF7L2, chromatin-remodelling genes such as TET2 and TET

59 ChIP-seq analysis revealed that TCF7L2 co-localizes with HNF4alpha and FOXA2 in HepG2 ce

60 Both SMAD1 and TCF7L2 co-occupy sites with master regulators adjacent t

61 TCF7L2 codes for the transcription factor TCF/LF, part o

62 transcriptional activity of the beta-catenin/TCF7L2 complex, whereas gamma-catenin down-regulates it.

63 f gene transcription beyond the beta-catenin/TCF7L2 complex.

64 he transcription factors ERG, SPI1, TCF4 and TCF7L2, components of the Ras signalling pathway, histon

65 t a highly conserved sequence in intron 5 of Tcf7l2 conceals an internal promoter region that, when a

66 Common variants in the gene TCF7L2 confer the largest effect on the risk of type 2 d

67 Although variants in TCF7L2 confer the strongest risk of T2D among common var

68 this study was to elucidate which variant in TCF7L2 confers diabetes susceptibility in African Americ

69 eviously that in gut endocrine L-cell lines, TCF7L2 controls transcription of the proglucagon gene (g

70 rvations, transgenic mice harboring multiple Tcf7l2 copies and overexpressing this gene display recip

71 ression may lead to diabetes, we developed a Tcf7l2 copy-number allelic series in mice.

72 One mechanism by which TCF7L2 could influence expression of genes involved in d

73 RNAs to beta-catenin or a dominant-negative TCF7L2 decreases both basal and Exd4-induced beta cell p

74 individual beta cells, were both lowered by Tcf7l2 deletion in islets from mice maintained on a high

75 oduce secreted factors, including BMP4, in a Tcf7l2-dependent manner to support beta-cell function.

76 In addition, we identified Tcf7l2-dependent pericytic expression of secreted factor

77 On the left, the parapineal prevents this Tcf7l2-dependent process, thereby promoting dHbl differe

78 s a transcription factor 7-like 2-dependent (TCF7L2-dependent) enhancer element that functions to inc

79 rt that the diabetes-associated variation in TCF7L2 did not associate with fasting EGP, insulin-induc

80 In that context, Tcf7l2 directly activates cholesterol biosynthesis genes

81 expression of a dominant negative isoform of TCF7L2 (dnTCF7L2) in interzone progeny, which may accoun

82 hese data indicate that genetic variation at TCF7L2 does not predispose an individual to type 2 diabe

83 smosomal partners, and with beta-catenin and TCF7L2, effectors of the canonical Wnt pathway.

84 Although TCF7L2 encodes TCF4, which cooperates with beta-catenin

85 Overexpression of TCF7L2 exerted minor inhibitory effects on glucose-regul

86 RESEARCH DESIGN AND TCF7L2 expression in rodent islets and beta-cell lines w

87 n pancreatic beta cells, despite evidence of TCF7L2 expression in various peripheral tissues importan

88 We define the effects of TCF7L2 expression level on mature beta-cell function and

89 Reducing TCF7L2 expression levels by RNAi decreased glucose- but

90 To further determine whether variation in Tcf7l2 expression may lead to diabetes, we developed a T

91 Restoring Tcf7l2 expression specifically in beta cells to endogeno

92 e of rs7903146 was associated with increased TCF7L2 expression, and decreased insulin content and sec

93 harbors cis-regulatory elements controlling TCF7L2 expression, we conducted in vivo transgenic repor

94 critical role for these enhancers in robust TCF7L2 expression.

95 In addition, both SMAD1 and TCF7L2 follow the binding of the predominant lineage reg

96 ing the fusion gene to be dependent on VTI1A-TCF7L2 for anchorage-independent growth using RNA interf

97 on proteins, including a fusion of VTI1A and TCF7L2 found in 3 out of 97 colorectal cancers.

98 ely activated in CRC tumors with compromised TCF7L2 function.

99 ound that the presumed cancer-promoting gene TCF7L2 functions instead as a transcriptional repressor

100 It is controversial whether Tcf4 (Tcf7L2) functions as an oncogene or tumor suppressor gen

101 ts in or near transcription factor 7-like 2 (TCF7L2), gastric inhibitory polypeptide receptor (GIPR),

102 Polymorphisms in the human TCF7L2 gene are associated with reduced insulin secretio

103 n-based samples suggest that variants in the TCF7L2 gene are associated with reduced kidney function

104 While deletion of the homologous murine Tcf7l2 gene throughout the developing pancreas leads to

105 TCF7L2 gene variants have been associated with increased

106 ested for modulation by polymorphisms of the TCF7L2 gene.

107 o harbored diabetogenic polymorphisms of the TCF7L2 gene.

108 riants in the transcription factor 7-like 2 (TCF7L2) gene are associated with chronic kidney disease

109 riants in the transcription factor 7-like 2 (TCF7L2) gene are consistently associated with type 2 dia

110 riants in the transcription factor 7-like 2 (TCF7L2) gene have been identified as the strongest genet

111 polymorphisms in the T-cell factor 7-like 2 (TCF7L2) gene, associated with T2D by genome-wide associa

112 ons were present within the ASTE1, HNF1A, or TCF7L2 genes, increasing even further when at least one

113 Effect modifications by TCF7L2 genetic polymorphisms are supported.

114 odds ratios (ORs) of T2D associated with the TCF7L2 genotype between high and low strata of GL (P = 0

115 ng and plasma glucose was independent of the TCF7L2 genotype.

116 SIGN AND Eight subjects with risk-conferring TCF7L2 genotypes (TT or TC at rs7903146) and 10 matched

117 n the group of subjects with risk-conferring TCF7L2 genotypes compared with control subjects.

118 n this population proved to be attenuated by TCF7L2 HapA (P-interaction = 0.01).

119 TCF7L2 HapA attenuates the positive association between

120 The objective was to investigate whether TCF7L2 HapA is associated with weight development and wh

121 tu hybridization histochemistry to show that TCF7L2 has a unique expression pattern in the mouse brai

122 y, these patterns of expression suggest that TCF7L2 has distinct functions within the brain, with a g

123 iple targets in key pathways may explain why TCF7L2 has emerged as the gene showing one of the strong

124 ymorphisms of transcription factor 7-like 2 (TCF7L2) have been associated with type 2 diabetes and BM

125 y and hepatic transcription factor 7-like 2 (TCF7L2) have generated opposing views.

126 es-associated variation at 20 loci including TCF7L2, HHEX-IDE, PPARG, KCNJ11, SLC30A8, IGF2BP2, CDKAL

127 To inactivate Tcf7l2 highly selectively in beta cells from the earlies

128 rs of oligodendrocyte differentiation (i.e., TCF7L2, ID2, and SOX2) and higher HAT transcript levels

129 otide polymorphisms (SNPs) in 12 loci (e.g., TCF7L2, IDE/KIF11/HHEX, SLC30A8, CDKAL1, PKN2, IGF2BP2,

130 Mutations in TCF7L2 identified from cancer genome sequencing efforts

131 s revealed an overlap of 20 genes, including TCF7L2, IGFBP2, CDKN2A, CDKN2B, GRB10, and PRC1.

132 d point to a previously unrecognized role of Tcf7l2 in control of cholesterol biosynthesis for CNS my

133 tests, no association between expression of TCF7L2 in eight types of human tissue samples and T2D-as

134 (rs7903146) for elevating the expression of TCF7L2 in human pancreas which may affect the regulation

135 Targeted disruption of Tcf7l2 in mice led to severe defects in oligodendrocyte

136 erestingly, the persistent overexpression of Tcf7l2 in non-pancreatic tissues results in a significan

137 ced in understanding the functional roles of TCF7L2 in pancreatic beta cells, despite evidence of TCF

138 Alternative splicing of TCF7L2 in pancreatic islets warrants future studies.

139 We also reveal a novel role of TCF7l2 in repressing a bone morphogenetic protein signal

140 t this hypothesis, we performed ChIP-seq for TCF7L2 in six human cell lines.

141 results support a central role of CDKAL1 and TCF7L2 in T2DM susceptibility in Southwest Asian populat

142 of hepatocytes, but the precise role of the TCF7L2 in this process is unknown.

143 the spatial-temporal expression patterns of TCF7L2, including expression in tissues involved in the

144 ed expression of TCF7L2DN, but not wild-type TCF7L2, increased gluconeogenesis and gluconeogenic gene

145 The diabetes-associated allele in TCF7L2 increases the rate of conversion to diabetes; how

146 significant variants in two loci CDKAL1 and TCF7L2, independent of sex, age and BMI, with leading va

147 A well accepted dogma is that TCF7l2 inhibits oligodendrocyte differentiation through

148 DAC1 and HDAC2 compete with beta-catenin for TCF7L2 interaction to regulate downstream genes involved

149 At the differentiation onset, Tcf7l2 interacts with a transcriptional co-repressor Kai

150 In the absence of an androgen signal, TCF7L2 interacts with FOXA1 at AR-binding sites and repr

151 This TCF7L2 intronic region contains several SNPs (rs7901695,

152 o BMI-association signals are present in the TCF7L2 intronic region of Hispanics, one of which is tag

153 chromatin sites and found that rs7903146, a TCF7L2 intronic variant strongly associated with type 2

154 Our findings suggest TCF7L2 is an important regulator of the hepatic phenotyp

155 A common genetic variation in TCF7L2 is associated with type 2 diabetes.

156 Tcf7l2 is essential for lateralized fate selection by ha

157 TCF7L2 is expressed in two distinct populations.

158 TCF7L2 is important in the development of peripheral org

159 TCF7L2 is involved in maintaining expression of beta-cel

160 mine whether the risk of T2D associated with TCF7L2 is modified by the glycemic load (GL), glycemic i

161 The type 2 diabetes risk gene TCF7L2 is the effector of the Wnt signaling pathway.

162 TCF7L2 is the strongest type 2 diabetes (T2D) locus iden

163 We report that TCF7l2 is upregulated transiently in postmitotic, newly

164 factor Tcf4 (transcription factor 7-like 2; Tcf7l2) is strongly expressed in connective tissue fibro

165 ts donors', we also show that the identified TCF7L2-ISL1 transcriptional network is regulated in a ge

166 ives the expression of dnTcf7l2, a truncated Tcf7l2 isoform that cannot bind beta-catenin and that th

167 Knockdown of TCF7L2 isoforms in mouse chondrocytes rescued hedgehog s

168 near 9 loci (NOTCH2, ADCY5, JAZF1, CDKN2A/B, TCF7L2, KCNQ1, MTNR1B, FTO, and HNF1B) were nominally as

169 (P(emp) < 0.05) at regional best SNPs in the TCF7L2, KLF14, and HMGA2 loci as well as suggestive sign

170 esults revealed that seven index SNPs at the TCF7L2, KLF14, KCNQ1, ADCY5, CDKAL1, JAZF1, and GCKR loc

171 hich were differentially expressed following Tcf7l2 knock-down.

172 Silencing Tcf7l2 led to a time-dependent appearance of 406 differe

173 Indirect gene regulation by TCF7L2 likely occurred via alternate transcription facto

174 y that a genetic variant harbored within the TCF7L2 locus impairs glucose tolerance through effects o

175 insulin secretion, genetic variation at the TCF7L2 locus may alter insulin action or directly modify

176 ly implicated noncoding variation within the TCF7L2 locus with type 2 diabetes (T2D) risk.

177 iation in the transcription factor 7-like 2 (TCF7L2) locus is associated with type 2 diabetes across

178 ypes as a result of manipulations leading to Tcf7l2 loss of function.

179 olymorphisms in 1 glucose and 4 lipids loci (TCF7L2, LPL, APOA5, CETP, and APOC1/APOE/TOMM40) signifi

180 ide insights as to how the overexpression of TCF7L2 may attenuate insulin secretion.

181 ociated variation (T allele at rs7903146) in TCF7L2 may impair the ability of hyperglycemia to suppre

182 d TCF7L2, and reveal important insights into TCF7L2-mediated gene regulation.

183 gulated SHROOM3 expression in a beta-catenin/TCF7L2-mediated manner, while SHROOM3 in turn facilitate

184 cyclin D1 gene promoter and MUC1-C promotes TCF7L2-mediated transcription by the recruitment of beta

185 inal-binding protein (CtBP), a suppressor of TCF7L2-mediated transcription.

186 nd miR-20a are up-regulated by CCAT2 through TCF7L2-mediated transcriptional regulation.

187 genesis, a recent study using liver-specific Tcf7l2(-/-) mice suggested the opposite.

188 How Tcf7l2 modifies beta-catenin signalling and controls mye

189 Interestingly, in MCF7 cells the TCF7L2 motif is enriched in most TCF7L2 sites but is not

190 The expression of TCF7L2 mRNA in pancreas was also elevated (~23-fold) amo

191 Additionally, TCF7L2 mRNA is expressed at moderate to low levels in sp

192 Our study shows that the short TCF7L2 mRNA variant in subcutaneous fat is regulated by

193 d by Vax2, drives transcription of truncated Tcf7l2 mRNAs.

194 In tcf7l2 mutants, most neurons on both sides differentiate

195 Tcf7l2 null mice also display enhanced glucose tolerance

196 studies demonstrated a repressive effect of TCF7L2 on hepatic gluconeogenesis, a recent study using

197 ally opposing cell-type specific effects for Tcf7l2 on the maintenance of balanced glucose metabolism

198 LP-1 and GIP but rather due to the effect of TCF7L2 on the sensitivity of the beta-cell to incretins.

199 few studies have investigated the effects of TCF7L2 on type 2 diabetes in the context of metabolic ri

200 se intolerance, to infer the contribution of Tcf7l2 overexpression in beta cells and in other tissues

201 n glucose tolerance in vivo, indicating that Tcf7l2 overexpression in beta cells does not account for

202 t account for the glucose intolerance in the Tcf7l2 overexpression mouse model.

203 several variants upstream and downstream of TCF7L2 (P < 0.003).

204 variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 x 10(-15)).

205 6 x 10(-12)), KCNQ1 (P = 1.35 x 10(-4)), and TCF7L2 (P = 5.10 x 10(-4)) with study-wise statistical s

206 e-wide level with rs12772424 in an intron of TCF7L2 (P=2.85E-8).

207 heterogeneity (FTO: P(DIFF) = 1.4 x 10(-7); TCF7L2: P(DIFF) = 4.0 x 10(-6)).

208 ay ranked top (nominal P = 0.0007, excluding TCF7L2; P = 0.002), containing a number of promising sin

209 regulation of a subset of metabolic genes by TCF7L2, particularly those involved in lipid and amino-a

210 These data demonstrate that Tcf7l2 plays a cell autonomous role in the control of be

211 Ac are also bound by TCF7L2, suggesting that TCF7L2 plays a critical role in enhancer activity.

212 These results directly demonstrate that Tcf7l2 plays a role in regulating glucose tolerance, sug

213 Collectively, these data posit that Tcf7l2 plays key roles in glucose metabolism through act

214 elevance of these findings for the action of TCF7L2 polymorphisms associated with Type 2 diabetes in

215 tion setting, we investigated the effects of TCF7L2 polymorphisms rs7903146 and rs12255372 and dietar

216 itional ablation, we found surprisingly that TCF7l2 positively regulates neonatal and postnatal mouse

217 tectable (RR 1.07 [0.97-1.19], P = 0.19) and TCF7L2 predominant (RR 1.53 [1.37-1.71], P = 1.3 x 10(-1

218 The encoded Tcf7l2 protein binds to DNA, but not beta-catenin, and t

219 nsion (CYP3A5, AGT, GNB3), diabetes (CAPN10, TCF7L2, PTPN22), prostate cancer (DG8S737, rs1447295), H

220 During oligodendrocyte maturation, Tcf7l2 recruits and cooperates with Sox10 to promote mye

221 t downregulation of TCF7L1 and its paralogue TCF7L2 reduces tumor growth in a xenograft model of huma

222 Here we define a stage-specific Tcf7l2-regulated transcriptional circuitry in initiating

223 Using RNA-sequencing, we have identified a TCF7L2-regulated transcriptional network responsible for

224 ansgenic reporter assays to characterize the TCF7L2 regulatory landscape.

225 Non-coding variation within TCF7L2 remains the strongest genetic determinant of type

226 RNA-seq analysis suggested that TCF7L2 represses transcription when tethered to the geno

227 y the physical interaction between CCAT2 and TCF7L2 resulting in an enhancement of WNT signaling acti

228 e use a humanized mouse model overexpressing Tcf7l2, resulting in glucose intolerance, to infer the c

229 eltaWC and DeltaWCBMI, regardless of FTO and TCF7L2 risk alleles.

230 Individuals with the TCF7L2 rs12255372 risk genotype may reduce body adiposit

231 Furthermore, the maternal genotype for TCF7L2 rs3814573 suggested an increased NTD risk among o

232 1.3 x 10(-13)), with only weak evidence for TCF7L2 (rs7901695 RR 1.21 [1.09-1.35], P = 0.001).

233 The strongest association was observed at TCF7L2 rs7903146 (odds ratio [OR] 1.30; P = 6.86 x 10(-)

234 ; HR, 5.70; 95% CI, 2.77-11.74; P < 0.0001), TCF7L2 rs7903146 (per each T allele; HR, 1.81; 95% CI, 1

235 TCF7L2 rs7903146 and rs10885406 were successfully genoty

236 In renal transplant patients, TCF7L2 rs7903146 is strongly and independently associate

237 We investigated whether FTO rs9939609 and TCF7L2 rs7903146 modified the association between the MD

238 significant interaction between the MDS and TCF7L2 rs7903146 on weight gain (P = 0.05), which sugges

239 We investigated the association between the TCF7L2 rs7903146 polymorphism and type 2 diabetes in 2,7

240 nificant evidence of association between the TCF7L2 rs7903146 polymorphism and type 2 diabetes risk i

241 less clear, but the effect may depend on the TCF7L2 rs7903146 variant.

242 The disease-associated variants in TCF7L2 (rs7903146) and WFS1 (rs10010131) have been shown

243 T16a insertion and the at-risk 'T' allele of TCF7L2 (rs7903146) for elevating the expression of TCF7L

244 8)), GCKR (rs1260326, P = 7.1 x 10(-11)) and TCF7L2 (rs7903146, P = 4.2 x 10(-10)) associated with 2-

245 TCF7L2(rs7903146) was identified as a complex effect or

246 luate whether transcription factor 7-like 2 (TCF7L2) rs7903146 gene polymorphism is associated with t

247 istage genome occupancy analyses reveal that Tcf7l2 serially cooperates with distinct co-regulators t

248 canonical Wnt signaling pathway mediated by TCF7L2 serves as a regulatory mechanism for oligodendroc

249 development of T2D through Wnt/beta-catenin/TCF7L2 signaling pathway.

250 ic attempts to enhance, rather than inhibit, TCF7l2 signaling to overcome arrested oligodendroglial d

251 Gene expression profiling in TCF7L2-silenced cells revealed increased levels of mRNA

252 to examine gene expression 3-96 h following Tcf7l2 silencing in rat hepatoma cells, and combined thi

253 Tcf7l2-silencing enhanced the expression and chromatin o

254 The risk of T2D associated with the TCF7L2 single nucleotide polymorphism did not significan

255 7 cells the TCF7L2 motif is enriched in most TCF7L2 sites but is not enriched in the sites bound by b

256 isms (SNPs) in or near genes (KCNJ11, PPARG, TCF7L2, SLC30A8, HHEX, CDKN2A/2B, CDKAL1, IGF2BP2, ARHGE

257 A fourth cluster (TCF7L2, SLC30A8, HHEX/IDE, CDKAL1, CDKN2A/2B) was define

258 One TCF7L2 SNP (rs7903146) showed compelling evidence of ass

259 This association between TCF7L2 splicing and plasma glucose was independent of th

260 assays to survey mRNA expression of multiple TCF7L2 splicing forms in up to 380 samples from eight ty

261 We tested whether the expression of TCF7L2 splicing forms was associated with single nucleot

262 urthermore, we determined the association of TCF7L2 splicing with the levels of plasma glucose and se

263 y both H3K4me1 and H3K27Ac are also bound by TCF7L2, suggesting that TCF7L2 plays a critical role in

264 hologically docked vesicles was unchanged by TCF7L2 suppression, secretory granule movement increased

265 In 3 of the 14 regions, TCF7L2 (T2D), CTLA4 (Graves' disease) and CDKN2A-CDKN2B

266 Expression levels of canonical Wnt/Tcf7l2 targets bone morphogenetic protein 7 and Wnt5b, w

267 We show that Tcf3 and Tcf7L2 (Tcf4) are required for proper ventral patterning

268 godendrocyte-restricted transcription factor TCF7L2/TCF4 as a bipartite co-effector of beta-catenin f

269 ion abolished the injury-induced increase in TCF7L2/TCF4+ cells, and protected oligodendrocytes from

270 Tcf7l2/Tcf4, a beta-catenin transcriptional partner, is

271 ansgenic mice that express dominant-negative TCF7L2 (TCF7L2DN) specifically in gcg-expressing cells.

272 ed the liver-specific dominant-negative (DN) TCF7L2 (TCF7L2DN) transgenic mouse model LTCFDN.

273 , KCNQ1, LOC387761, MTNR1B, NOTCH2, SLC30A8, TCF7L2, THADA, and TSPAN8-LGR5.

274 light novel mechanisms of gene regulation by TCF7L2 that involve interplay between multiple hepatic t

275 so and Sox10 that sequentially interact with Tcf7l2 to coordinate the switch at the transitions of di

276 s analysis suggested that GATA3 might tether TCF7L2 to the genome at these sites.

277 erential binding of the transcription factor TCF7L2 to the rs6983267 risk allele over the non-risk.

278 The TCF7L2 transcription factor is linked to a variety of hu

279 erminal subunit (MUC1-C) associates with the TCF7L2 transcription factor.

280 Polymorphisms of the gene TCF7L2 (transcription factor 7-like 2) are strongly asso

281 insulin secretion, consistent with the extra TCF7L2 translocating beta-catenin from the plasma membra

282 nvasion-driver genes, 17 of which, including TCF7L2, TWIST2, MSH2, DCC, EPHB1 and EPHB2 have been pre

283 Two vertebrate TCFs (TCF-1/TCF7 and TCF-4/TCF7L2) use the C-clamp as an alternatively spliced doma

284 sts that changes in risk attributable to the TCF7L2 variant are magnified under conditions of increas

285 The TCF7L2 variant rs7903146 appears to affect risk of type

286 The TCF7L2 variant was associated with all three maternal gl

287 Maternal GCK and TCF7L2 variants are associated with glucose levels known

288 ight enhance the risk of T2D associated with TCF7L2 variants.

289 enotyped at five (ARIC) and two (FHS) common TCF7L2 variants.

290 The diabetes risk allele at TCF7L2 was associated with a stronger effect on peak ins

291 Inactivation of pericytic Tcf7l2 was associated with impaired expression of genes

292 A previous association of CFRD with SNPs in TCF7L2 was replicated in this study (P = 0.004; combined

293 Transgenic mice in which Tcf7l2 was selectively inactivated in their pancreatic p

294 rs12255372 (in TCF7L2) was associated with lower BMI in both MESA (beta

295 ity variants near ADRA2A, KCNJ11, KCNQ1, and TCF7L2 were associated with reduced depolarization-evoke

296 in (TEAD) and transcription factor 7-like 2 (TCF7L2), which are transcription factors of the Hippo an

297 regulates beta-catenin and its binding with TCF7L2, which in turn is critical for the production of

298 uantity modified risk of T2D associated with TCF7L2, which suggests that changes in risk attributable

299 ession of the Wnt pathway mediator Tcf4 (aka Tcf7l2) within OLPs is specific to lesioned-but not norm

300 Gata2, Gata3, Klf2, Lrp5, Ppargamma2, Sfrp1, Tcf7l2, Wnt10b, and Wnt3a.