ライフサイエンスコーパス: ZEB2

1 0) and zinc finger E-box binding homeobox 2 (ZEB2).

2 regulation of Ednrb expression by SOX10 and ZEB2.

3 bronectin as well as EMT regulators ZEB1 and ZEB2.

4 by downregulating its target genes, ZEB1 and ZEB2.

5 on of miR-205 and its target genes, ZEB1 and ZEB2.

6 expression of miR-200a target genes ZEB1 and ZEB2.

7 anscriptional repressors, including ZEB1 and ZEB2.

8 C-modulating miRNAs is inhibited by Zeb1 and Zeb2.

9 r E-box-binding homeobox factor 1 (ZEB1) and ZEB2.

10 with ZV in repressing Zp via binding ZEB1 or ZEB2.

11 consistent with increased expression of ZEB1/ZEB2.

12 ses EMT by repressing expression of ZEB1 and ZEB2.

13 in turn, led to increased expression of ZEB1/ZEB2.

14 of miR-221 upregulates GAX and downregulates ZEB2.

15 ts ability to downregulate the expression of ZEB2.

16 type, partially through suppressing ZEB1 and ZEB2.

17 in treatment through suppression of Slug and ZEB2.

18 alysis revealed Id2 to be a direct target of Zeb2.

19 next expressed miR-221 in ECs and identified ZEB2, a modulator of the epithelial-mesenchymal transiti

20 of the mice had retroviral integrations near Zeb2, a transcriptional corepressor leading to overexpre

21 Zeb2 activation appears to be a key step in the EMT proc

22 cute lymphoblastic leukemia, suggesting that Zeb2 activation promotes the transformation of CALM-AF10

23 apitulating miR-221 expression or inhibiting ZEB2 activation.

24 interaction with HDAC1/2-NuRD and abolishes Zeb2 activity for SC differentiation.

25 ression, mediated by the zinc-finger protein Zeb2 (also known as Sip1), is essential for differentiat

26 We found that Zeb2 (also named Sip1, Zfhx1b), a zinc finger transcript

27 uman/mouse VISTA enhancer (62 kb upstream of Zeb2) also up-regulated the Zeb2 promoter, providing evi

28 e that zinc-finger E-box-binding homeobox 2 (Zeb2, also called Sip1) transcription factor is a critic

29 ation are both perturbed, demonstrating that Zeb2, although undetectable in adult Schwann cells, has

30 through its impaired ability to inhibit ZEB1/ZEB2 and acquired concomitant ability to repress new tar

31 lly, we identified the E-cadherin regulators ZEB2 and BMI1 as likely miR-708 targets.

32 o-mesenchymal transition (EMT) markers ZEB1, ZEB2 and CDH2 (which encodes N-cadherin).

33 lase KDM1A as a novel interaction partner of ZEB2 and demonstrated that mouse and human T-ALLs with i

34 Mice with combined mutations in Zeb2 and Edn3 (double mutants) had more severe enteric a

35 w gene fusions and focal deletions of MBNL1, ZEB2 and ELF1, were disproportionately prevalent in youn

36 p of PPP1R1A-regulated gene set with that of ZEB2 and EWS, which regulates metastasis and neuronal di

37 sion of IL-1beta, Ccl2, Cxcl5, Snail1, Zeb1, Zeb2 and Foxf1.

38 wth, accompanied by upregulation of SLUG and ZEB2 and increased invasive properties.

39 transcriptional regulators such as Snail and ZEB2 and is sufficient to drive the transition to epithe

40 ated through the opposite regulation of ZEB1/ZEB2 and miR-200b and miR-200c.

41 We speculate that the actions of GH on ZEB2 and P- and E-cadherin expression play a role in the

42 ssion of miR-200 decreased the expression of Zeb2 and Pkd1 in HNF-1beta mutant cells.

43 The expression of miR-200 targets, Zeb2 and Pkd1, was increased in HNF-1beta knock-out kidn

44 rations, consistent with the hypothesis that Zeb2 and Ras pathway activation promotes B-lineage leuke

45 d RNA polymerase II localization and reduced Zeb2 and Snail1 binding to epithelial gene promoters.

46 ZEB2 and T-bet cooperate to switch on a terminal CTL dif

47 t miR-192 downregulates expression of Bcl-2, Zeb2 and VEGFA in vitro and in vivo, which is responsibl

48 Smad2 and Smad5 form a complex with Zeb2 and Ywhab/14-3-3beta and Ywhag/14-3-3gamma form a c

49 te-stage NK-cell maturation including T-BET, ZEB2, and BLIMP-1 without affecting viability or prolife

50 These targets include SIAH1, SETD2, ZEB2, and especially FOXN3, which we demonstrated for th

51 expression of E- and P-cadherins, targets of ZEB2, and inhibited E-cadherin promoter activity.

52 the DNA-binding transcription factors Zeb1, Zeb2, and Klf4.

53 ssion profiling assay, we identified Twist1, Zeb2, and PDGFRalpha and beta as Foxq1 downstream target

54 s, suggesting cooperativity among CALM-AF10, Zeb2, and Ras pathway mutations.

55 Dicer-KO CDs, its direct target genes Zeb1, Zeb2, and Snail2 are upregulated, and miRNA-depleted CDs

56 zinc finger E-box binding homeobox protein, ZEB2, and the down-regulation of miR-200b and miR-200c.

57 a receptor TGFBR2 and the EMT inducers ZEB1, ZEB2, and the snail transcriptional repressor SNAI2, eac

58 e HIF-1alpha expression and attenuated Zeb1, Zeb2, and Twist expression.

59 jor EMT regulatory genes (Snai1, Slug, Zeb1, Zeb2, and Twist1) involved in EMT.

60 binding (ZEB) transcription factors ZEB1 and ZEB2, and undergo EMT on TGF-beta stimulation.

61 o negatively regulate the expression of ZEB1/ZEB2, and we found that the expression of miR-200s was l

62 ociated gene expression of Snail1, Zeb1, and Zeb2; and down-regulated E-cadherin.

63 Zeb2 antagonizes inhibitory effectors including Notch an

64 This indicated that 2 copies of Zeb2 are required for EDN3 to prevent neuronal different

65 ade could also operate in human as T-bet and Zeb2 are similarly regulated in mouse and human NK cells

66 finger E-box-binding (ZEB) proteins ZEB1 and ZEB2 are transcription factors essential in TGF-beta-med

67 data, we identified the transcription factor ZEB2 as a novel AML dependency.

68 l-mesenchymal transition (EMT) and establish ZEB2 as a novel regulator of AML proliferation and diffe

69 nc finger E-box-binding transcription factor ZEB2 as a recurrent genetic lesion in immature/ETP-ALL.

70 This study reveals ZEB2 as an oncogene in the biology of immature/ETP-ALL a

71 We identified Slug and ZEB2 as direct functional targets of miR-218.

72 e miR-200 family and their targets, ZEB1 and ZEB2, as unique P(4)/PR-mediated regulators of uterine q

73 human UBC cells through the TGFbeta1-ZEB2NAT-ZEB2 axis.

74 Our results extend the role of ZEB2 beyond regulating epithelial-mesenchymal transition

75 Mutation of ZEB2 binding sites on the E-cadherin promoter abolished

76 matin immunoprecipitation, we identified two ZEB2 binding sites that modulate the ability of ZEB2 to

77 of key EMT and CSC genes, including TWIST1, ZEB2, BMI1, and POU5F1.

78 EDN3, Zeb2(+/+) EPCs continued expression of ZEB2 but did not undergo any neuronal differentiation.

79 s have detailed microRNA-mediated control of Zeb2, but little is known about the genomic context of t

80 Knockdown of ZEB2, but not ZEB1, led to EBV lytic reactivation.

81 transcriptionally regulated by NF-kappaB and ZEB2, but not ZEB1.

82 ation, establishing that timely induction of Zeb2 by T-bet is an essential event during NK cell diffe

83 Both ZEB1 and ZEB2 can bind Zp via the ZV element.

84 Thus, we conclude that either ZEB1 or ZEB2 can play a central role in the maintenance of EBV l

85 Here we show that the transcription factor Zeb2 cell-autonomously represses Smad signalling to limi

86 creased neuronal differentiation compared to Zeb2(+/+) cells.

87 Zeb2 chromatin immunoprecipitation analysis revealed Id2

88 reased expression of c-Met, fibronectin, and Zeb2 compared with Huh7 and Hep3B cells, which have an e

89 Therefore, Zeb2 controls SC maturation by recruiting HDAC1/2-NuRD c

90 sults indicate that the transcription factor Zeb2 controls the expression of molecules thereby regula

91 nd by T-bet, and this binding was altered by ZEB2 deficiency.

92 Zeb2-deficient Schwann cells continuously express repres

93 Zeb2 deletion arrests SCs at an undifferentiated state d

94 mice with a Zeb2 loss-of-function mutation (Zeb2(Delta)) and mice carrying a spontaneous recessive m

95 Zeb2(Delta/+) EPCs had increased neuronal differentiatio

96 Overexpression of EDNRB in Zeb2(Delta/+) EPCs restored inhibition of neuronal diffe

97 Incubation of Zeb2(Delta/+) EPCs with EDN3, on the other hand, resulte

98 EPCs) or were heterozygous for the mutation (Zeb2(Delta/+) EPCs) were exposed to EDN3; we analyzed th

99 In parallel, Edn3(ls) mice were crossed with Zeb2(Delta/+)mice; intestinal tissues were collected fro

100 ZEB2 depletion impaired the proliferation of both human

101 The transcription factors SOX10 and ZEB2 directly activated the EDNRB promoter.

102 , mice in which CD11c(+) cells overexpressed Zeb2 displayed a reduction in cDC1s.

103 subtype of human leukemia and possibly other ZEB2-driven malignancies.

104 Moreover, Zeb2-driven mouse leukaemia exhibit some features of the

105 aggressive subtype of human T-ALL using our Zeb2-driven mouse model.

106 in the repression of E-cadherin by ZEB1 and ZEB2 during EMT, thereby enhancing migration and invasio

107 Putative miR-200-regulated genes included Zeb2, enriched 3.5-fold in the pull down.

108 When exposed to EDN3, Zeb2(+/+) EPCs continued expression of ZEB2 but did not

109 al differentiation, similar to incubation of Zeb2(+/+) EPCs with EDN3.

110 embryos that expressed only wild-type Zeb2 (Zeb2(+/+) EPCs) or were heterozygous for the mutation (Z

111 the epithelial state by suppressing the Zeb1/Zeb2 epithelial gene transcriptional repressors.

112 zinc finger transcription factors, ZEB1 and ZEB2, execute EMT programs in embryonic development and

113 in influx assay, shRNA-mediated knockdown of ZEB2 expression abrogated this effect.

114 Attenuation of ZEB2 expression activates the PI3K/AKT pathway, enhances

115 cells consistently showed increased ZEB1 and ZEB2 expression and decreased E-cadherin expression.

116 by LKB1 loss in lung ADC, which upregulates ZEB2 expression and represses DNp63 transcription in a d

117 n with small interfering RNA (siRNA) reduced Zeb2 expression and resulted in decreased FcepsilonRI-me

118 PTEN ceRNA, and demonstrates that abrogated ZEB2 expression cooperates with BRAF(V600E) to promote m

119 This suggests that low Zeb2 expression differentially regulates signaling pathw

120 n mouse model, we demonstrate that sustained Zeb2 expression initiates T-cell leukaemia.

121 This was caused by both a dependence of Zeb2 expression on T-bet and a probable cooperation of t

122 GH-dependent increase in ZEB2 expression results in loss of P- and E-cadherins in

123 two microRNAs known to downregulate ZEB1 and ZEB2 expression.

124 migration and invasion by promoting ZEB1 and ZEB2 expression.

125 fects p53-regulated EMT by altering ZEB1 and ZEB2 expression.

126 egulated miR-192 family members also repress ZEB2 expression.

127 cing of the miR-200 family microRNAs affects ZEB2 expression.

128 thelial mesenchymal transition: VIM, TGFss1, ZEB2, FOXC1, CXCR4, were striking compared to cell lines

129 rin in the chick, but both Snail factors and Zeb2 fulfil a similar role in chick and mouse in directl

130 T-bet overexpression could not fully bypass ZEB2 function.

131 The signal localizes to intron 2 of the ZEB2 gene (zinc finger E box-binding homeobox 2).

132 The zinc-finger, E-box-binding homeobox-2 (Zeb2) gene encodes a SMAD-interacting transcription fact

133 , JUP, MED15, MED9, PTPRE SREBF1, TOP2A, and ZEB2, genes that interact with established CHD proteins

134 In humans, SIP1 (ZEB2) haploinsufficiency leads to Mowat-Wilson syndrome,

135 including Twist1, Snail1, Snail2, ZEB1, and ZEB2, have been shown to induce epithelial mesenchymal t

136 siRNA knockdown of ZEB1 and ZEB2 impaired As-transformed p53lowHBEC migration and in

137 Mice conditionally lacking Zeb2 in CD11c(+) cells had a cell-intrinsic reduction in

138 ell function was preserved, but mice lacking Zeb2 in NK cells were more susceptible to B16 melanoma l

139 We conclude that GH increases expression of ZEB2 in part by increasing expression of a ZEB2 natural

140 Mice lacking Zeb2 in Schwann cells develop a severe peripheral neurop

141 Transgenic expression of Zeb2 in Tbx21(-/-) NK cells partially restored a normal

142 Haploinsufficiency of Zeb2 in this developmental context reflects inheritance

143 R-200 family and down-regulation of ZEB1 and ZEB2 in two different mouse models of preterm labor.

144 resses E-cadherin expression by upregulating Zeb2, in part, through a microRNA-mediated mechanism and

145 B resulted in the loss of TWIST1, SNAI2, and ZEB2 induction, and a failure of cells to invade and met

146 r findings suggest that genetic variation in ZEB2 influences the risk of RCC.

147 Excitingly, we observed that ZEB1 and ZEB2 inhibit expression of the contraction-associated ge

148 A total of 91% (10 of 11) of mice with Zeb2 insertions developed B-lineage acute lymphoblastic

149 More than half of the mice with Zeb2 integrations also had Nf1 integrations, suggesting

150 entified, all of which occurred in mice with Zeb2 integrations, consistent with the hypothesis that Z

151 n mouse model, we recently demonstrated that ZEB2 is an oncogenic driver of immature T-cell acute lym

152 When Zeb2 is deleted in adult mice, Schwann cells readily ded

153 Zeb2 is known to control epithelial to mesenchymal trans

154 structs and an inhibitor, we determined that ZEB2 is upregulated by serum and downregulates GAX, whil

155 box binding homeobox transcription factor-2 (ZEB2) is correlated with poor prognosis and patient outc

156 ein complex through direct disruption of the ZEB2-KDM1A interaction or pharmacological inhibition of

157 miR-200 expression and Zeb2 knockdown are known to inhibit cell invasion in in

158 However, Zeb2 knockdown does not fully recapitulate miR-200c over

159 n of miR-192 and p53, via the miR-192 target Zeb2, leading to augmentation of downstream events relat

160 ion by downregulating expression of ZEB1 and ZEB2, leading to production of infectious virus.

161 Experimental knockdown of Zeb2 leads to an increase in BMP-Smad-dependent axon gro

162 Zeb2 levels are downregulated in the embryonic rodent mi

163 d that mouse and human T-ALLs with increased ZEB2 levels critically depend on KDM1A activity for surv

164 ere observed between miR-218 levels and Slug/ZEB2 levels in cancer tissue samples.

165 stablished that the GH-dependent increase in ZEB2 levels is associated with increased transcription o

166 We performed studies in mice with a Zeb2 loss-of-function mutation (Zeb2(Delta)) and mice ca

167 E-cadherin) and mesenchymal (vimentin, ZEB1, ZEB2) markers and decreased aggressiveness as judged by

168 , YAP is inactivated, which in turn relieves ZEB2-mediated default repression of DNp63 and triggers s

169 rmore, the loss of Mel-18 promoted ZEB1- and ZEB2-mediated downregulation of E-cadherin transcription

170 We show that ZEB2 modulates PTEN protein levels in a microRNA-depende

171 putative microRNA decoys for PTEN, validates ZEB2 mRNA as a bona fide PTEN ceRNA, and demonstrates th

172 concentrations, T-bet induced expression of Zeb2 mRNA, which then triggered CTLs to adopt terminally

173 ctivity in peripheral neuropathies caused by ZEB2 mutations.

174 associated with increased transcription of a ZEB2 natural antisense transcript required for efficient

175 f ZEB2 in part by increasing expression of a ZEB2 natural antisense transcript.

176 idbrain dopaminergic neurons, in conditional Zeb2 (Nestin-Cre based) knockout mice.

177 ions at 19 common insertion sites, including Zeb2, Nf1, Mn1, Evi1, Ift57, Mpl, Plag1, Kras, Erg, Vav1

178 Moreover, the immature phenotype of Zeb2(-/-) NK cells closely resembled that of Tbx21(-/-)

179 in EBV-positive cells containing both ZEBs, ZEB2, not ZEB1, was the primary ZEB family member bound

180 ke Claudin 23, and to EMT inducer genes like Zeb2, Notch2 and Gli2.

181 via their effects on expression of ZEB1 and ZEB2 of the switch between latent and lytic infection by

182 A mutant miR-221 fails to downregulate ZEB2 or upregulate GAX.

183 on or antagonism of its target genes (Bcl-2, Zeb2 or VEGFA) may have considerable therapeutic potenti

184 Thus, the coordinated actions of T-bet and ZEB2 outline a novel genetic pathway that forces commitm

185 transcription by the EMT inducers Snail1 and Zeb2 plays a fundamental role in defining embryonic terr

186 The transcription factor Sip1 (Zeb2) plays multiple roles during CNS development from e

187 KZF3 (AIOLOS), TBX21 (T-bet), NFIL3 (E4BP4), ZEB2, PRDM1 (BLIMP1), and RORA mRNA levels are higher in

188 The transcription factors ZEB1 and ZEB2 promote EMT.

189 e, derived from the deleted region, enhanced Zeb2 promoter activity in transcription assays.

190 2 kb upstream of Zeb2) also up-regulated the Zeb2 promoter, providing evidence of a string of conserv

191 E2F1 on vimentin, fibronectin, and ZEB1 and ZEB2 promoters.

192 Therefore, targeting the ZEB2 protein complex through direct disruption of the ZE

193 at the border of the SMAD-binding domain of ZEB2 protein induces ribosomal pausing and compromises p

194 sion of cancer cells, as well as reduced the ZEB2 protein level.

195 ively correlated with ZEB2NAT transcript and ZEB2 protein levels in human bladder cancer specimens.

196 n, we describe a novel mechanism that limits ZEB2 protein synthesis.

197 Thus, we conclude that Zeb2 regulates commitment to both the cDC2 and pDC linea

198 ibe a novel transgenic rodent model in which Zeb2 regulatory sequence has been disrupted, resulting i

199 r by P-cadherin We also show that Snail2 and Zeb2 repress P-cadherin transcription in the primitive s

200 Reciprocally, ectopic expression of Zeb2 resulted in a higher frequency of mature NK cells i

201 Targeted deletion of Zeb2 resulted in impaired NK cell maturation, survival,

202 of lung cancer in part by modulation of Slug/ZEB2 signaling, and provide a potential therapeutic stra

203 y showed that the cellular proteins ZEB1 and ZEB2/SIP1 both play key roles in regulating the latent-l

204 actors, TWIST1, SNAI1/Snail1, SNAI2/Slug and ZEB2/Sip1, and are highly invasive.

205 , another zinc finger E-box-binding protein, ZEB2/SIP1, is the key player.

206 The Zeb2 siRNA-treated mast cells had altered cell cycle pro

207 iptional repressors ZEB1 (TCF8/deltaEF1) and ZEB2 (SMAD-interacting protein 1 [SIP1]/ZFXH1B).

208 senchymal transition (EMT) markers vimentin, Zeb2, Snail, and Twist.

209 of some transcription repressors, like Zeb1, Zeb2, Snail, and Twist.

210 f EMT-associated transcription factors ZEB1, ZEB2, Snail, Slug, and Twist.

211 s expression of the known EMT inducers ZEB1, ZEB2, Snail1, and transforming growth factor beta2 (TGFB

212 genome-wide transcriptome analysis reveals a Zeb2 target gene encoding the Notch effector Hey2 as a p

213 maturation such as Sox2 and Ednrb emerge as Zeb2 target genes, supporting its function as an 'inhibi

214 of other EMT-inducing TFs, with Twist, Zeb1, Zeb2, TGF-beta1, and FOXC2 being commonly induced.

215 expression of the E-Box repressors ZEB1 and ZEB2, thereby opposing TGF-beta-mediated downregulation

216 f the mesenchymal genes, as well as ZEB1 and ZEB2, through the mediation of the E2F1 transcription fa

217 2 binding sites that modulate the ability of ZEB2 to downregulate GAX promoter activity.

218 -cadherin by transcriptional upregulation of ZEB2 to stimulate cell invasion.

219 tified zinc finger E-box-binding homeobox 2 (ZEB2) to be up-regulated in a GH dose- and time-dependen

220 the TF zinc finger E box-binding homeobox 2 (Zeb2) to play a crucial role in regulating DC developmen

221 EN ceRNAs and further characterized one, the ZEB2 transcript.

222 pt required for efficient translation of the ZEB2 transcript.

223 corepressor leading to overexpression of the Zeb2-transcript.

224 oRNAs repress both the EMT-inducing ZEB1 and ZEB2 transcription factors.

225 Mechanistically, we showed that ZEB2 transcriptionally represses genes that regulate mye

226 Strikingly, a genetic Zeb2 variant associated with Mowat-Wilson syndrome disru

227 Zeb2 was expressed from the pre-pDC and pre-cDC stage on

228 Expression of EMT genes TWIST and ZEB2 was increased in sensitive xenografts, suggesting a

229 Inverse correlation between miR-192 and Zeb2 was observed in glomeruli of human subjects with ea

230 we found that the transcription factor (TF) Zeb2 was the most highly induced TF during NK cell matur

231 factors known to activate EMT, both ZEB1 and ZEB2 were upregulated following mTOR repression.

232 ger E-box binding homeobox proteins ZEB1 and ZEB2, which act as transcriptional repressors.

233 gulate E-cadherin by directly targeting ZEB1/ZEB2, which are transcriptional repressors of E-cadherin

234 ression through direct targeting of ZEB1 and ZEB2, which encode transcriptional repressors of E-cadhe

235 regulating the cellular transcription factor Zeb2, which represses the transcription of BZLF1.

236 e of their downstream targets, SIP1 (ZFHX1B, ZEB2), whose protein product suppresses E-cadherin expre

237 ed with a 12 kb deletion, 1.2 Mb upstream of Zeb2, within a 4.1 Mb gene desert.

238 an be mediated by activation of the ZEB1 and ZEB2 (ZEB) transcription factors, which repress miR-200

239 d from embryos that expressed only wild-type Zeb2 (Zeb2(+/+) EPCs) or were heterozygous for the mutat

240 Herein we demonstrate that the Zfhx1b (Sip1, Zeb2) zinc finger homeobox gene is required in the MGE,