ライフサイエンスコーパス: TCF-1

1 TCF-1 acted through both GATA-3-dependent and GATA-3-ind

2 TCF-1 has been recently shown to critically regulate mem

3 TCF-1 is highly expressed in the earliest thymic progeni

4 TCF-1 or stabilized beta-catenin greatly stimulated acti

5 TCF-1 thus has dual roles, i.e., acting cooperatively wi

6 TCF-1 was directly associated with the Eomes allele and

7 TCF-1 was intrinsically required for the differentiation

8 erentiation, was induced by T cell factor 1 (TCF-1) and its cofactor beta-catenin, mainly from the pr

9 signaling in the intestine, T-cell factor 1 (TCF-1) and TCF-4, have opposing functions.

10 hancer factor 1 (LEF-1) and T cell factor 1 (TCF-1) are closely related transcription factors that ar

11 T cell factor 1 (TCF-1) is a transcription factor known to act downstream

12 T-cell factor 1 (TCF-1), a related transcription factor, contains a simil

13 t ILC2 development required T cell factor 1 (TCF-1, the product of the Tcf7 gene), a transcription fa

14 hat a transcription factor, T-cell factor 1 (TCF-1; also known as transcription factor 7, T-cell spec

15 study, we demonstrate that T cell factor 1 (TCF-1; encoded by Tcf7), a transcription factor also imp

16 identified, e.g., GATA3 and T cell factor-1 (TCF-1) (gene name Tcf7).

17 T cell factor-1 (TCF-1) and lymphoid enhancer factor-1 (LEF-1), members o

18 T cell factor-1 (TCF-1) and lymphoid enhancer-binding factor 1, the effec

19 nscription factor 7 (TCF7) (T cell factor-1 (TCF-1)) are downstream effectors of the WNT signaling pa

20 ression of CD27, CXCR3, and T cell factor-1 (TCF-1), each a marker that is individually correlated wi

21 We examined the role of a LEF-1/TCF-1 binding site in the human adenosine deaminase (ADA

22 nalysis demonstrated that a functional LEF-1/TCF-1 binding site is not required for enhancer-mediated

23 Mutation of the LEF-1/TCF-1 site destroyed the ability of the ADA enhancer/loc

24 he hypothesis that factors binding the LEF-1/TCF-1 site play an architectural role during the in vivo

25 ncer in transgenic mice with a mutated LEF-1/TCF-1 site.

26 201-bp core promoter region and Sp1, NRE-2a, TCF-1/LEF-1, and Sp1/NF-AT binding sites in the upstream

27 a stabilized beta-catenin (beta-cat(Tg)), a TCF-1 activator.

28 g site located within the enhancer abrogated TCF-1 and beta-catenin-mediated activation of CD4 report

29 In addition, TCF-1 as well as beta-catenin were able to stimulate tra

30 Together, these data show that LEF-1 and TCF-1 are redundant in the regulation of T cell differen

31 LEF-1 and TCF-1 coordinated such differentiation by two general me

32 Thus, LEF-1 and TCF-1 differ in several aspects of nuclear localization.

33 t, the subcellular localization of LEF-1 and TCF-1 fused to green fluorescent protein (GFP)) was exam

34 LEF-1 and TCF-1 immunostaining can serve to identify specific subt

35 e evidence for a redundant role of LEF-1 and TCF-1 in Wnt signaling during mouse development.

36 CF-1 (P < 0.0001), suggesting that LEF-1 and TCF-1 transcription factor expression may be lost in Th2

37 been proposed for the HMG proteins LEF-1 and TCF-1.

38 model where Notch signals induce TCF-1, and TCF-1 in turn imprints the T-cell fate by upregulating e

39 2, Msx-1, serum response elements, SP-1, and TCF-1.

40 wever, including E proteins, Myb, Gfi-1, and TCF-1.

41 Cxcr5 expression and, together with Bcl6 and TCF-1, formed a transcriptional circuit that guided TFC

42 ing the interaction between beta-catenin and TCF-1.

43 tes the interaction between beta-catenin and TCF-1.

44 ired the transcription factors Bcl6, E2A and TCF-1 but was inhibited by the transcriptional regulator

45 e transcription factors RORalpha, GATA3, and TCF-1 and produce the type 2 cytokines IL-4, IL-5, IL-9,

46 cases of T-ALL/LyL express LEF-1 as well as TCF-1, exhibiting uniform nuclear immunostaining for bot

47 those encoding transcription factors Bcl11b, TCF-1 (Tcf7), and HEBalt, Notch target Deltex1, Deltex3L

48 Both TCF-1(-/-) and RORgammat(-/-) DP thymocytes underwent si

49 d EBP50 stabilized conventional beta-catenin/TCF-1 complexes and connected beta-catenin to dnTCF-1 to

50 Moreover, beta-catenin/TCF-1 directly interacted with the RORgammat promoter re

51 demonstrate that, like IL-7Ralpha and CD62L, TCF-1 and lymphoid enhancer-binding factor 1 exhibit dyn

52 In colon cancer cells, TCF-1 is predominantly cytoplasmic.

53 In contrast, CD4 levels were restored on DP TCF-1(-/-) cells by transgenic expression of a wild-type

54 ic lymphoma (T-ALL/LyL) was found to express TCF-1, and we find that 9 of 10 cases of T-ALL/LyL expre

55 rom apoptosis, whereas ectopically expressed TCF-1 was not able to rescue the defective T cell develo

56 We show that the transcription factor TCF-1 is required for the efficient generation of all kn

57 the long isoform of the transcription factor TCF-1.

58 The transcription factors TCF-1 and LEF-1 are essential for early T cell developme

59 inhibit expression of transcription factors TCF-1, LEF-1, and RORgammat that are required for the IS

60 Whereas CD8+ effectors deficient for TCF-1 and LEF-1 retained the capacity to express IFN-gam

61 1 and 32 of 42 (76%) were immunoreactive for TCF-1, including most cases of angioimmunoblastic lympho

62 ngs demonstrate an essential requirement for TCF-1 in ILC2 differentiation and reveal a link among Tc

63 ad decreased survival, suggesting a role for TCF-1 in promoting survival in the nonlymphoid tissues.

64 The complete spectra of regulatory roles for TCF-1 and LEF-1 in CD8+ T cell responses are yet unknown

65 Furthermore, TCF-1 blocked T(H)1 fate by negatively regulating interf

66 eadily localizes to the nucleus, whereas GFP-TCF-1 remains in the cytoplasm.

67 Several reports now reveal how TCF-1 and GATA-3 are mobilized in early T cells and the

68 Our studies thus identify TCF-1 as a critical player in a transcriptional program

69 ymocytes, we demonstrated that deficiency in TCF-1 and LEF-1 diminished the output of CD4(+) T cells

70 Mice deficient in TCF-1 displayed significantly reduced protein and mRNA l

71 RORgammat was significantly downregulated in TCF-1(-/-) thymocytes that underwent accelerated apoptos

72 +) ILC3 showed a dose-dependent reduction in TCF-1 expression.

73 s of other hematopoietic lineages, including TCF-1 and GATA-1.

74 a suggest a model where Notch signals induce TCF-1, and TCF-1 in turn imprints the T-cell fate by upr

75 demonstrate that IL-7R signals also inhibit TCF-1 and LEF-1 expression in mature peripheral T cells.

76 Instead, TCF-1 physically interacted with Runx3 to cooperatively

77 phase, the Ag-specific CD8+ T cells lacking TCF-1 and LEF-1 exhibited an effector phenotype and were

78 Moreover, TCF-1-deficient memory CD8(+) T cells were progressively

79 SL), GATA-3, E2A/HEB and Id proteins, c-Myb, TCF-1, and members of the Runx, Ets, and Ikaros families

80 4 enhancer was detected in wild-type but not TCF-1 null mice by chromatin-immunoprecipitation analysi

81 ter, and they severely impair the ability of TCF-1 to regulate growth in colon cancer cells.

82 Furthermore, activation of TCF-1 by stabilized beta-catenin was able to enhance DP

83 ogenitors (EILPs) expressing high amounts of TCF-1.

84 ession circuits of Gfi1 against Egr-2 and of TCF-1 against PU.1 as proposed elsewhere, but requires a

85 CD8+ T cells in the peritoneal cavity of TCF-1-deficient mice had decreased survival, suggesting

86 a stabilized beta-catenin, a coactivator of TCF-1, resulted in up-regulation of CD4.

87 and by combination with germline deletion of TCF-1, we found that loss of both factors completely abr

88 indicating that RORgammat acts downstream of TCF-1 in the regulation of DP thymocyte survival.

89 Forced expression of TCF-1 in bone marrow progenitors partially bypassed the

90 maintains a balance between the two forms of TCF-1 is unclear.

91 in this study we show additional function of TCF-1/beta-catenin pathway in the regulation of CD4 expr

92 program begins earlier with the induction of TCF-1 (Tcf7 gene product) and GATA-3.

93 colon cells, a dominant-negative isoform of TCF-1 (dnTCF-1) is expressed that is equally distributed

94 r example, alternatively spliced isoforms of TCF-1 and TCF-4 with a C-terminal "E" tail are uniquely

95 nce of crypt stem cells, whereas knockout of TCF-1 leads to adenomas.

96 cl-2 restored survival but not CD4 levels of TCF-1(-/-) DP cells.

97 Furthermore, loss of TCF-1 and LEF-1 unexpectedly caused derepression of CD4

98 Loss of TCF-1 expression impaired the capacity of these ILC subs

99 Finally, recruitment of TCF-1 to CD4 enhancer was detected in wild-type but not

100 The role of TCF-1 and LEF-1 in the CD4-versus-CD8 lineage 'choice' w

101 lts are reminiscent of the critical roles of TCF-1 in early T cell development.

102 Our results suggest that upregulation of TCF-1 expression denotes the earliest stage of ILC fate

103 early locus 'poising' function dependent on TCF-1 and GATA-3, a stochastic-permissivity function dep

104 l lymphoma, were immunoreactive for LEF-1 or TCF-1 (P < 0.0001), suggesting that LEF-1 and TCF-1 tran

105 ich encode the transcription factor LEF-1 or TCF-1, respectively) resulted in T(FH) cell defects, whi

106 The vast majority of LEF-1+ and/or TCF-1+ PTCL (34 of 39 or 87%) exhibit a composite Th1 T-

107 s (48%), are immunoreactive for LEF-1 and/or TCF-1, with 36 of 38 cases immunoreactive for both, indi

108 Enforced expression of a p45 TCF-1 isoform limited the expansion of Ag-specific CD8 T

109 forced expression of Eomes partly protected TCF-1-deficient memory CD8(+) T cells from time-dependen

110 nhances CD4 expression in vivo by recruiting TCF-1 to stimulate CD4 enhancer activity.

111 expression of RORgammat successfully rescued TCF-1(-/-) DP thymocytes from apoptosis, whereas ectopic

112 ns with Notch signaling, and roles of Runx1, TCF-1, and Hes1, providing bases for a comprehensively u

113 isolated a further member of this subfamily (TCF-1) from zebrafish.

114 In this study, we show that LEF1 and TCF7 (TCF-1) are not only expressed in thymocytes, but also in

115 y, we first identify Socs1, Socs3, and Tcf7 (TCF-1) as gene targets that are negatively regulated by

116 ads to the down-regulation of LEF1 and TCF7 (TCF-1) expression in human naive CD8 T cells.

117 erentially express inhibitory LEF1 and TCF7 (TCF-1) isoforms and that T cell activation changes the i

118 act ILC or NK cell development, GATA3, TCF7 (TCF-1), AHR, SOX4, RUNX2, and ZEB1 transcript levels are

119 soform balance in favor of stimulatory TCF7 (TCF-1) isoforms.

120 Two vertebrate TCFs (TCF-1/TCF7 and TCF-4/TCF7L2) use the C-clamp as an alter

121 We further demonstrated that TCF-1 directly repressed LEF-1 expression in early thymo

122 Therefore, our data demonstrated that TCF-1 enhances DP thymocyte survival through transcripti

123 Unexpectedly, we found that TCF-1-deficient (Tcf7(-/-)) mice developed aggressive T

124 We also showed that TCF-1 and LEF-1 were dispensable for T cell lineage comm

125 Here we showed that TCF-1 deficiency limited proliferation of CD8(+) effecto

126 The TCF-1 and LEF-1 transcription factors are known to play

127 and specificity for the LEF-1 NLS versus the TCF-1 NLS.

128 Further characterization of these TCF-1-induced cells revealed expression of many T-lineag

129 Thus, TCF-1 and LEF-1 adopted distinct genetic 'wiring' to pro

130 Thus, TCF-1 and LEF-1 cooperatively regulate generation of mem

131 Thus, TCF-1 initiates T(H)2 differentiation of activated CD4(+

132 Thus, TCF-1-regulated survival and CD4 expression are two sepa

133 Transfer of the LEF-1 NLS to TCF-1 can confer pendulin/Rch1 binding, demonstrating th

134 Normal colonic epithelia express a truncated TCF-1 form, called dnTCF-1, that lacks the critical beta

135 on of a wild-type TCF-1, but not a truncated TCF-1 that lacks a domain required for interacting with

136 ells by transgenic expression of a wild-type TCF-1, but not a truncated TCF-1 that lacks a domain req

137 Most importantly, when TCF-1 is forcibly expressed in bone marrow (BM) progenit

138 suggest that TCF-4 is Wnt-promoting, whereas TCF-1 acts like a tumor suppressor.

139 equence showed distinct subregions, in which TCF-1 sites and a conserved element were required for T-

140 associated with the Eomes allele and the Wnt-TCF-1 pathway was necessary and sufficient for optimal E

141 Zebrafish TCF-1 is expressed throughout zebrafish embryonic develo

142 The protein product of zebrafish TCF-1 (zTCF-1), shares sequence similarity with the mamm