ライフサイエンスコーパス: HNF-6

1 hologs of other mammalian genes regulated by hnf-6.

2 r that is a functional ortholog of mammalian hnf-6.

3 e mediated in part by the phosphorylation of HNF-6.

4 Cotransfection assays demonstrate that HNF-6 activates expression of a reporter gene driven by

5 es reporter gene expression, suggesting that HNF-6 activates transcription of these promoters.

6 xamined the effects of BHPC-specific loss of HNF-6 alone and within the background of BHPC-specific l

7 Knockdown of zebrafish hnf-6 alters expression of vhnf1 and the zebrafish ortho

8 sruption of the onecut transcription factor, hnf-6, alters mammalian biliary system development.

9 er there is a functional interaction between HNF-6 and FoxA2.

10 y 18 of gestation and in the adult pancreas, HNF-6 and HNF-3 beta transcripts colocalize in the exocr

11 More detailed analysis of HNF-6 and HNF-3 beta's developmental expression patterns

12 We show that HNF-6 and HNF-3 possess different DNA binding specificit

13 of staged specific embryos demonstrate that HNF-6 and its potential target gene, HNF-3 beta, are coe

14 To define the genetic interaction between HNF-6 and Notch signaling in an in vivo mouse model, we

15 HNF-6 and Notch signaling interact in vivo to control ex

16 his in vivo model, simultaneous loss of both HNF-6 and RBP-J results in down-regulation of both HNF-1

17 These experiments strongly suggest that hnf-6 and vhnf1 function within an evolutionarily conser

18 h signaling and hepatocyte nuclear factor-6 (HNF-6) are two genetic factors known to affect lineage c

19 Hepatocyte nuclear factor 6 (HNF-6) belongs to the family of One Cut transcription fa

20 HNF-6 binding activity was also found in the intestinal

21 ogous fusion gene; a mutation that abolished HNF-6 binding also abolished the stimulatory effect of P

22 which is similar to the recently identified HNF-6 binding sequence 5'-DHWATTGAYTWWD-3' (where W = A

23 Using the HNF-6 binding sequence DHWATTGAYTWWD (where W = A or T,

24 ntial target genes, we selected seven of the HNF-6 binding sequences and demonstrated that they bind

25 expression of a reporter gene driven by the HNF-6 binding site from either the HNF-3 beta or transth

26 This HNF-6 binding site was able to confer a stimulatory effe

27 Because CYP7A1 contains potential HNF-6 binding sites in its promoter region, we tested th

28 nal epithelial cell line HT29, and potential HNF-6 binding sites were present in intestinal sucrase i

29 The deletion of HNF-3 and HNF-6 binding sites within the LCR reduced histone acety

30 HNF-6 binds to DNA as a monomer utilizing a single cut d

31 HNF-6, but not HNF-3 beta, expression continues in the p

32 e consensus PKA phosphorylation sites in the HNF-6 carboxyl terminus markedly reduced this phosphoryl

33 ith recombinant adenovirus vector expressing HNF-6 cDNA by growth hormone treatment leads to an induc

34 d the yeast one-hybrid system to isolate the HNF-6 cDNA, which encodes a cut-homeodomain-containing t

35 tions with recombinant adenovirus expressing HNF-6 complementary DNA (cDNA) (AdH6).

36 with HNF-6 was dependent on retention of the HNF-6 Cut domain LXXLL sequence, which mediated recruitm

37 d that this protein interaction required the HNF-6 Cut-Homeodomain and FoxA2 winged-helix DNA binding

38 Furthermore, we show that the HNF-6 Cut-Homeodomain sequences were sufficient to syner

39 represses HNF-6 transcription by inhibiting HNF-6 DNA binding activity.

40 Increasing hepatic levels of HNF-6 either by infection with recombinant adenovirus ve

41 and hepatocytes and that maintaining hepatic HNF-6 expression hinders the normal biliary proliferativ

42 Our results showed that HNF-6 expression is diminished in BEC and hepatocytes an

43 hepatoma (HepG2) cells with either HNF-3 or HNF-6 expression vectors show that only HNF-6 provided s

44 HNF-6 expression was observed only in crypt epithelia ex

45 le of a liver-enriched transcription factor (HNF-6) functioning as a coactivator protein to potentiat

46 ucose transporter 2 (Glut-2), as well as the HNF-6, HNF-3, HNF-1alpha, HNF-4alpha, and C/EBPalpha tra

47 al for CYP7A1 transcriptional stimulation by HNF-6 in cotransfection assays.

48 ic interaction involving Notch signaling and HNF-6 in mice has been inferred through separate experim

49 Isolated loss of HNF-6 in this mouse model fails to demonstrate a phenoty

50 vestigation revealed that PKA phosphorylated HNF-6 in vitro.

51 To directly evaluate if HNF-6 is a transcriptional activator for CYP7A1, we used

52 We also found that HNF-6 is also abundantly expressed in the dorsal root ga

53 In the liver, HNF-6 is expressed not only in hepatocytes, but also in

54 Hepatocyte nuclear factor 6 (HNF-6) is a member of the one cut family of transcriptio

55 This suggests that diminished hepatic HNF-6 levels are required for repair in response to bili

56 ranscription factor, suggesting that reduced HNF-6 levels contribute to diminished HNF-3beta-specific

57 We found that maintaining hepatic HNF-6 levels with AdH6 infection resulted in significant

58 However, when HNF-6 loss is combined with RBP-J loss, a phenotype cons

59 These studies suggest that HNF-6 may regulate hepatocyte-specific genes and may pla

60 biliary cells are sensitive to the dosage of hnf-6-mediated gene transcription.

61 e examined the hepatic expression pattern of HNF-6 messenger RNA (mRNA) and protein after bile duct l

62 ously shown that hepatic expression of mouse HNF-6 messenger RNA (mRNA) and protein significantly dec

63 afish vhnf1 rescues the biliary phenotype of hnf-6 morphants.

64 ct ligation, we demonstrated that diminished HNF-6 mRNA levels correlate with a reduction in CYP7A1 m

65 mammals, the OC family is comprised of OC-1/HNF-6, OC-2, and OC-3.

66 Forced expression of either hnf-6 or vhnf1 also produces biliary phenotypes.

67 Antisense-mediated knockdown of zebrafish hnf-6 perturbs development of the intrahepatic biliary s

68 esent study to determine whether maintaining HNF-6 protein expression during AdHNF3beta infection pre

69 In conclusion, the HNF-6 protein is a component of the complex network of h

70 To maintain hepatic HNF-6 protein levels during BDL liver injury, we used mo

71 We found that HNF-6 protein levels in BEC and hepatocytes were diminis

72 n, we propose a biologic role for diminished HNF-6 protein levels in bile duct disease.

73 t obstruction was associated with diminished HNF-6 protein levels.

74 binding assays showed that only recombinant HNF-6 protein, but not the HNF-3 proteins, binds to the

75 binds with the same specificity as the liver HNF-6 protein.

76 equences and demonstrated that they bind the HNF-6 protein.

77 Furthermore, C/EBPbeta and HNF-6 proteins bound to the 3'RE region (+4647/+4694 bp)

78 3 or HNF-6 expression vectors show that only HNF-6 provided significant transcriptional activation of

79 e data suggest that at a FoxA-specific site, HNF-6 serves as a coactivator protein to enhance FoxA2 t

80 Site-directed mutagenesis of the HNF-6 sites in the HNF-3(beta) and transthyretin promote

81 o enhance FoxA2 transcription, whereas at an HNF-6-specific site, FoxA2 represses HNF-6 transcription

82 se in hepatic Glut-2 levels, suggesting that HNF 6 stimulates in vivo transcription of the Glut-2 gen

83 pG2) cotransfection assays demonstrated that HNF-6 synergistically stimulated FoxA2 but not FoxA1 or

84 -3gamma, -4gamma, and -6 and the mapping of HNF-6 to chromosome bands 15q21.1-21.2 by fluorescence i

85 promoter by interfering with the binding of HNF-6 to its target DNA sequence.

86 s at an HNF-6-specific site, FoxA2 represses HNF-6 transcription by inhibiting HNF-6 DNA binding acti

87 hibited diminished hepatic expression of the HNF-6 transcription factor, suggesting that reduced HNF-

88 d with reduced levels of the Cut-Homeodomain HNF-6 transcription factor, we conducted the present stu

89 increased FoxA2 levels caused a decrease in HNF-6 transcriptional activation of the glucose transpor

90 patic Glut-2 promoter is a direct target for HNF-6 transcriptional activation.

91 omoter region, we tested the hypothesis that HNF-6 transcriptionally regulates CYP7A1.

92 fact that FoxA2 transcriptional synergy with HNF-6 was dependent on retention of the HNF-6 Cut domain

93 To evaluate the in vivo function of HNF-6, we examined the hepatic expression pattern of HNF

94 ified a liver-enriched transcription factor, HNF-6, which is required for HNF-3 beta promoter activit

95 ntify a liver-enriched transcription factor, HNF-6, which recognizes the -138 to -126 region of the H

96 methylation interference, we predicted that HNF-6 will bind to 22 additional hepatocyte-enriched gen