ライフサイエンスコーパス: HNF-1alpha

1 HNF-1alpha augmented the Cdx2-induced but not Cdx1-induc

2 HNF-1alpha homozygous knockout mice exhibit a renal Fanc

3 HNF-1alpha is a major transcriptional regulator of many

4 HNF-1alpha is a transcription factor that helps in the t

5 HNF-1alpha patients showed far greater variation in fast

6 HNF-1alpha-mutated lesions could be distinguished from o

7 HNF-1alpha-mutated lesions had the lowest lesion signal

8 HNF-1alpha-null mice are viable but sterile and exhibit

9 atory lesions compared with four of 21 (19%) HNF-1alpha-mutated, seven of 14 (50%) unclassified, and

10 Hepatocyte nuclear factor-1a (HNF-1alpha) is a transcription factor that plays an impo

11 naling via hepatocyte nuclear factor 1alpha (HNF-1alpha) compared with controls, which reduced expres

12 ons in the hepatocyte nuclear factor 1alpha (HNF-1alpha) gene have been described as sensitive to the

13 tations in hepatocyte nuclear factor 1alpha (HNF-1alpha) lead to maturity-onset diabetes of the young

14 tations in hepatocyte nuclear factor 1alpha (HNF-1alpha).

15 mutations in hepatic nuclear factor 1alpha (HNF-1alpha).

16 ons in the hepatocyte nuclear factor-1alpha (HNF-1alpha) gene cause maturity onset diabetes of the yo

17 finger and hepatocyte nuclear factor-1alpha (HNF-1alpha) homeodomain transcription factors are expres

18 activator hepatocyte nuclear factor-1alpha (HNF-1alpha) is essential for DNA binding and association

19 ion factor hepatocyte nuclear factor-1alpha (HNF-1alpha) located on chromosome 12q.

20 Hepatocyte nuclear factor-1alpha (HNF-1alpha) mutations are the most common cause of matur

21 s encoding hepatocyte nuclear factor-1alpha (HNF-1alpha) or HNF-4.

22 etion, and hepatocyte nuclear factor-1alpha (HNF-1alpha), a transcription factor involved in tissue-s

23 tations in hepatocyte nuclear factor-1alpha (HNF-1alpha).

24 e encoding hepatocyte nuclear factor-1alpha (HNF-1alpha, which is encoded by the gene TCF1).

25 ter 2 (Glut-2), as well as the HNF-6, HNF-3, HNF-1alpha, HNF-4alpha, and C/EBPalpha transcription fac

26 atic levels of glycogen, Glut-2, HNF-3gamma, HNF-1alpha, and HNF-4alpha at 2 and 3 days postinfection

27 rs, hepatocyte nuclear factors 1alpha and 4 (HNF-1alpha and HNF-4).

28 s, including 45 GCK mutation carriers and 40 HNF-1alpha mutation carriers.

29 nd that the normal activation of HNF-4alpha, HNF-1alpha, and PGC-1 induced by fasting is attenuated i

30 ively regulated the expression of HNF-4alpha/HNF-1alpha and their downstream targets, implicating a r

31 a acts as a negative regulator of HNF-4alpha/HNF-1alpha demonstrating that HNF-3alpha and HNF-3beta h

32 iabetes of the young (MODY) criteria was 63% HNF-1alpha, 2% HNF-4alpha, 0% IPF-1, 1% HNF-1beta, 0% Ne

33 lled DCoH) for the transcriptional activator HNF-1alpha.

34 icient in hepatocyte nuclear factor 1 alpha (HNF-1alpha) were produced by use of the Cre-loxP recombi

35 heterozygous HNF-1alpha mutations lead to an HNF-1alpha-dependent impairment of apoM expression.

36 amilies in which diabetes segregates with an HNF-1alpha mutation.

37 ion in both GCK (48% controls, P<0.0001) and HNF-1alpha (42% controls, P<0.0001).

38 ein by day 7, and expressed CK18, HNF-4, and HNF-1alpha on days 14-28.

39 Here, we demonstrate that GATA-5 and HNF-1alpha physically associate both in vivo and in vitr

40 In contrast to the glucokinase and HNF-1alpha genes, mutations in the HNF-4alpha gene are a

41 or(HNF)-4alpha/MODY1, glucokinase/MODY2, and HNF-1alpha/MODY3 genes can cause this form of diabetes.

42 The Tcf1 protein (also known as HNF-1alpha) also regulates transcription of the gene (Nr

43 Despite structural similarity between HNF-1alpha and -1beta, HNF-1beta mutation carriers have

44 with HNF-1alpha and inducing DNA binding by HNF-1alpha.

45 36 patients, either with diabetes caused by HNF-1alpha mutations or type 2 diabetes, who were matche

46 GATA/HNF-1alpha cooperativity is mediated by HNF-1alpha through its activation domains, which are ori

47 In conclusion, HNF-1alpha mutation carriers have a mutation-specific de

48 stable interface that further distinguishes HNF-1alpha from other flexible POU-homeodomain proteins.

49 al uncoupling was significantly higher in DN-HNF-1alpha cells, such that rates of ATP synthesis were

50 termediates revealed a negative impact of DN-HNF-1alpha and Hnf-1alpha knock-out on mitochondrial sec

51 changes the response to hypoglycaemic drugs; HNF-1alpha diabetes has marked sulphonylurea sensitivity

52 In contrast to an earlier HNF-1alpha-null mouse line that had been produced by use

53 the cells with expression plasmids encoding HNF-1alpha or HNF-4.

54 cofactor (DCoH) for the transcription factor HNF-1alpha.

55 ng site which binds the transcription factor HNF-1alpha.

56 ctionally related hepatocyte nuclear factors HNF-1alpha and HNF-4alpha play a critical role in normal

57 for expression of the transcription factors HNF-1alpha and PXR within the fetal liver.

58 ng domain ligated to the coding sequence for HNF-1alpha, HNF-1beta, HNF-3, or HNF-4 completely restor

59 We hypothesize that GATA/HNF-1alpha cooperativity is mediated by HNF-1alpha throu

60 poM expression in vivo and that heterozygous HNF-1alpha mutations lead to an HNF-1alpha-dependent imp

61 mutational hotspot, we cocrystallized human HNF-1alpha 83-279 with a high-affinity promoter and solv

62 ganization and partial sequence of the human HNF-1alpha gene.

63 -1beta subjects but was suppressed by 89% in HNF-1alpha subjects (P = 0.004) and 80% in control subje

64 Serum levels of apoM were decreased in HNF-1alpha/MODY3 subjects when compared with control sub

65 zide and the biguanide metformin differed in HNF-1alpha diabetes and type 2 diabetes, and to investig

66 roinsulin-to-insulin ratios are increased in HNF-1alpha subjects (29.5%) but not in GCK (18.5%) subje

67 GCK patients (2.4+/-1.8 mmol/l) but large in HNF-1alpha patients (8.5+/-3.0 mmol/l, P< 0.0001).

68 Mutations in HNF-1alpha are associated with maturity-onset diabetes o

69 vestigate whether patients with mutations in HNF-1alpha mutations (MODY3) have reduced serum apoM lev

70 The numerous diabetes-causing mutations in HNF-1alpha thus identified a previously unrecognized POU

71 ralesional steatosis was exclusively seen in HNF-1alpha-mutated lesions.

72 1 cells overexpressing doxycycline-inducible HNF-1alpha dominant-negative (DN-) gene mutations, and i

73 In mice, HNF-1alpha was required for claudin-2 expression in the

74 ent by CDP of two hepatic activators, namely HNF-1alpha and C/EBPalpha, that bind to three different

75 we measured apoM levels in the serum of nine HNF-1alpha/MODY3 patients, nine normal matched control s

76 We observed no HNF-1alpha mutations among 86 unrelated late-onset diabe

77 tients including 29 new families and 8 novel HNF-1alpha gene mutations.

78 We have identified four novel HNF-1alpha missense mutations in MODY3 families.

79 at these polymorphisms affect the binding of HNF-1alpha and glucocorticoid receptor to the promoter,

80 Deletion of HNF-1alpha activation domains or interruption of HNF-1-b

81 coh2) Dcoh2, which increases dimerization of HNF-1alpha.

82 stal structure of the dimerization domain of HNF-1alpha (HNF-p1).

83 ion G20R perturbs the dimerization domain of HNF-1alpha, an intertwined four-helix bundle.

84 variants that are deficient in expression of HNF-1alpha and HNF-4.

85 Expression of HNF-1alpha in proximal tubules may protect against cysto

86 ys, indicating an organ-specific function of HNF-1alpha in the regulation of claudin-2 gene expressio

87 inger of GATA factors and the homeodomain of HNF-1alpha.

88 bjects with different types and locations of HNF-1alpha mutations did not reveal genotype-phenotype c

89 n secretion with either mutations or loss of HNF-1alpha.

90 ogenetic effect is consistent with models of HNF-1alpha deficiency, which show that the beta-cell def

91 Here, the dimerization motif of HNF-1alpha is shown to form an intermolecular four-helix

92 ted the mechanism of metabolic regulation of HNF-1alpha/FXR signaling.

93 tor superfamily and an upstream regulator of HNF-1alpha expression.

94 To assess the roles of HNF-1alpha and HNF-4 in gene activation and chromatin re

95 SIRT1 regulated HNF-1alpha/FXR signaling partially through dimerization

96 HNF-1beta and the structurally related HNF-1alpha bind specifically to the Pkhd1 promoter and s

97 n total HNF1A transcript levels but residual HNF-1alpha protein activity in G319S homozygotes may sti

98 ients, nine normal matched control subjects (HNF-1alpha(+/+)), and nine HNF-4alpha/MODY1 subjects.

99 a higher age at diagnosis (42.7 years) than HNF-1alpha (20.4 years), HNF-1beta (24.2 years), or HNF-

100 This study demonstrates that HNF-1alpha is required for apoM expression in vivo and t

101 Serological tests indicated that HNF-1alpha was present in complexes throughout the day,

102 h HNF-4alpha/MODY1 subjects, indicating that HNF-1alpha haploinsufficiency rather than hyperglycemia

103 Our ChIP assay shows that HNF-1alpha and glucocorticoid receptor have stronger aff

104 The HNF-1alpha patients had a generalized aminoaciduria with

105 The HNF-1alpha patients had glucosuria at lower glycemic con

106 tylation depends on interactions between the HNF-1alpha/HNF-4 signaling cascade and the serpin LCR.

107 ndividuals, suggesting that mutations in the HNF-1alpha gene are a common cause of diabetes in German

108 Heterozygous mutations in the HNF-1alpha gene are responsible for maturity-onset diabe

109 We have also identified the mutation in the HNF-1alpha gene in the Jutland pedigree, one of the orig

110 Analyses of linked DNA polymorphisms in the HNF-1alpha gene indicated that the Pro291fsinsC mutation

111 93% controls, P = 0.78) but increased in the HNF-1alpha subjects (134.5% controls, P = 0.005).

112 In mice lacking the HNF-1alpha gene, insulin secretion and intracellular cal

113 ize the functional heterodimerization of the HNF-1alpha and HNF-1beta proteins.

114 re, we describe the crystal structure of the HNF-1alpha dimerization domain at 1.7 A resolution and a

115 perturb distinct structural features of the HNF-1alpha domain.

116 The information on the sequence of the HNF-1alpha gene and its promoter region will facilitate

117 s confirm the functional significance of the HNF-1alpha regulatory elements that had previously been

118 table defect of glucose sensing, whereas the HNF-1alpha mutation causes a progressive defect that alt

119 Thus, HNF-1alpha and HNF-4 control both chromatin structure an

120 tion carriers have hyperinsulinemia, whereas HNF-1alpha mutation carriers have normal or reduced insu

121 fect has been identified in individuals with HNF-1alpha mutations.

122 tylate Dcoh2, promoting its interaction with HNF-1alpha and inducing DNA binding by HNF-1alpha.

123 Patients with HNF-1alpha diabetes had a 5.2-fold greater response to g

124 Patients with HNF-1alpha diabetes had a strong insulin secretory respo

125 eralized aminoaciduria seen in patients with HNF-1alpha mutations is a general feature of patients wi

126 measured in urine samples from patients with HNF-1alpha mutations, age-matched nondiabetic control su

127 lucosuria and aminoaciduria in patients with HNF-1alpha mutations.

128 f [6,6-(2)H(2)]glucose, in six subjects with HNF-1alpha mutations, six subjects with HNF-1beta mutati