ライフサイエンスコーパス: Pit-1

1 Pit-1 and Ets-1 binding to a composite element synergist

2 Pit-1 and Pit-1beta constitute such a pair of transcript

3 Pit-1 enhances the Ras signaling pathway to the prolacti

4 Pit-1 interaction with the Pitx2 C terminus masks the in

5 Pit-1 interacts with CCAAT/enhancer-binding protein alph

6 Pit-1 is essential for the establishment of these lineag

7 Pit-1, a member of the POU domain family of transcriptio

8 Pit-1, a pituitary-specific POU homeodomain transcriptio

9 Pit-1/GHF-1 is a pituitary-specific, POU homeodomain tra

10 Pit-1/TR synergy is therefore a consequence of a novel s

11 ry-specific positive transcription factor 1 (Pit-1), leading to excessive PRL secretion.

12 they express the transcription factor GHF-1 (Pit-1) but not growth hormone (GH) or prolactin (PRL).

13 hormone and the transcription factor GHF-1 (Pit-1).

14 e gibbon ape leukemia virus receptor Glvr-1 (Pit-1) or the amphotropic retrovirus receptor Ram-1 (Pit

15 ns, including phospho-CREB, JUN/FOS, GATA-1, Pit-1, and EKLF, failed to stimulate HAT activity.

16 homology to the transcription factors Oct-1, Pit-1, and POU-M1.

17 g known transcription factors, such as Sp-1, Pit-1, glucocorticoid receptor, and hypoxia-inducible fa

18 action surface in Ets-1, which reduced Ets-1/Pit-1 binding in vitro, did not significantly affect Ets

19 e we show that the organization of the Ets-1/Pit-1 composite element tolerates significant flexibilit

20 olecular features: organization of the Ets-1/Pit-1 composite element, physical interaction of these t

21 he rPRL promoter via the most proximal GHF-1/Pit-1 binding site, footprint I, and synergized with GHF

22 itary-specific, POU-homeodomain factor GHF-1/Pit-1 is necessary, but not sufficient, for cell-specifi

23 with the transcription factors Oct-1 and -2, Pit-1, and POU-M1.

24 ssing TtT-97 thyrotropes by cotransfecting a Pit-1 expression vector.

25 ed with bona fide binding sites for either a Pit-1 monomer or dimer, and these sites tolerated a sepa

26 tocyte nuclear factor-1beta (HNF-1beta) is a Pit-1, Oct-1/2, Unc-86 (POU) homeodomain-containing tran

27 tocyte nuclear factor-1beta (HNF-1beta) is a Pit-1, Oct-1/2, UNC-86 (POU)/homeodomain-containing tran

28 omposite Pit-1/ETS protein-binding site or a Pit-1 element with no known affinity for ETS proteins re

29 in dysmorphogenesis and failure to activate Pit-1 gene expression.

30 Mechanistically, although Pit-1-mediated SMC calcification was not associated with

31 Both Oct-1 and Pit-1 bind the B29 3' enhancer in in vitro electrophoret

32 w that the physical interaction of Ets-1 and Pit-1 is not required for Ras responsiveness or synergy

33 amino acid differences between the Oct-1 and Pit-1 POUs domains is the key determinant for the differ

34 ogated binding of both recombinant Pit-1 and Pit-1-containing nuclear extracts revealed that the two

35 scription factors, including Sp1, Zn-15, and Pit-1, predictable and developmentally appropriate expre

36 CBP and Pit-1 acted synergistically in TRH stimulation of the TS

37 Therefore, df and Pit-1 are both cell-autonomous factors required for thyr

38 Expression of both C/EBPalpha and Pit-1 in CHO cells is required for high basal transcript

39 ed GH genes, co-expression of C/EBPalpha and Pit-1 synergistically activated the transfected rGH prom

40 Thus, both C/EBPalpha and Pit-1 were required for high basal transcription while i

41 is required for Pitx2-Pit-1 interaction and Pit-1 synergism.

42 action with partner proteins such as NLI and Pit-1.

43 ll line, which expresses prolactin (PRL) and Pit-1, but not the T3 receptor (TR) or GH, was used as a

44 In summary, Ras responsiveness and Pit-1/Ets-1 synergy are mediated through the assembly of

45 ifferential use of distinct TAD subtypes and Pit-1 TAD subregions to mediate either synergy or Ras re

46 fective in DNA binding, transactivation, and Pit-1 synergism activities, did not suppress the wild ty

47 analyses, the NPC in HSMCs was identified as Pit-1 (Glvr-1), a member of the novel type III NPCs.

48 nd can synergize with other factors, such as Pit-1, to regulate gene expression.

49 ces acetylation of other substrates, such as Pit-1.

50 s, affected the dynamic interactions between Pit-1 and C/EBPalpha in different ways.

51 isrupts the cooperative interactions between Pit-1 and ETS-1 and blocks the induction of Pit-1-depend

52 The mutant Pitx2 protein binds Pit-1, but there was no detectable synergism on the prol

53 t with gibbon ape leukemia retrovirus (binds Pit-1 receptor), indicating that Pit-2 is the form of Na

54 Cotransfection of both Pit-1 and GATA-2 into CV-1 cells synergistically stimula

55 Additionally, the presence of both Pit-1 and Pit-1beta in pituitary cells allows diverse in

56 d transcriptional activation domains of both Pit-1 and TR reduced Pit-1/TR synergy in parallel with t

57 aneous infection with vectors targeting both Pit-1 and Pit-2 yielded transduction efficiencies consis

58 the POU homeodomain, which is common to both Pit-1 and Pit-1beta.

59 signaling in the anterior pituitary via both Pit-1-dependent and -independent pathways, yielding diff

60 When both Pit-1 and GATA-2 were combined, a slower migrating compl

61 the hGH LCR allosterically program the bound Pit-1 complex for chromatin activating functions.

62 ast, the hGH-N transgene is not activated by Pit-1 sites native to either the hGH-N or rat (r)GH gene

63 Activation by Pit-1 was dependent on the same Pit-1 sites shown to be

64 otection that differed from that produced by Pit-1.

65 deletion or mutation were not stimulated by Pit-1.

66 NA binding analysis using either a composite Pit-1/ETS protein-binding site or a Pit-1 element with n

67 In contrast, Pit-1 sites at the hGH-N promoter are consistently unabl

68 type III sodium-dependent P(i) cotransporter Pit-1 and certain osteoblast and chondrocyte genes (tiss

69 rix GLA protein, the phosphate cotransporter Pit-1, a calcium-sensing receptor related factor, osteop

70 II sodium-dependent phosphate cotransporter, Pit-1, in SMC calcification in vitro.

71 on of the type III Na(+)/P(i) cotransporters Pit-1 and Pit-2.

72 SMC-iRNA had decreased Pit-1 mRNA and protein levels and sodium-dependent phosp

73 Further analyses revealed decreased Pit-1 and increased Lef-1 expression in the mutant mouse

74 Conversely, deletion of the defined Pit-1 TAD (amino acids 2-80) retained synergy, but not R

75 nal Ets binding sites (EBS): a composite EBS/Pit-1 element located at -212 and an EBS that co-localiz

76 xtracts of TtT-97 thyrotropes, which express Pit-1, footprinted this proximal region with a pattern o

77 ription from an inactive locus, we expressed Pit-1 in nonpituitary cell types.

78 Human SMC stably expressing Pit-1 small interfering double-stranded RNA (SMC-iRNA) w

79 eas the pituitary-specific POU domain factor Pit-1 activates growth hormone gene expression in one ce

80 ted by the tissue-specific POU domain factor Pit-1, which is initially expressed on Embryonic Day 13.

81 he pituitary-specific POU homeodomain factor Pit-1.

82 teins, such as the pituitary-specific factor Pit-1, are members of the homeodomain family of proteins

83 the pituitary-specific transcription factor Pit-1 (official nomenclature, POU1F1).

84 The transcription factor Pit-1 (POU1-F1) plays a dominant role in cell lineage ex

85 The POU domain transcription factor Pit-1 is expressed in somatotropes, lactotropes, and thy

86 the pituitary-specific transcription factor Pit-1 to the hGH-N promoter and a selective decrease in

87 he pituitary POU domain transcription factor Pit-1 within this segment.

88 he co-expression of the transcription factor Pit-1, which removes C/EBPalpha from the heterochromatic

89 the pituitary-specific transcription factor Pit-1.

90 the pituitary-specific transcription factor Pit-1.

91 ites for the POU domain transcription factor Pit-1.

92 the pituitary-specific transcription factor, Pit-1, and the thyroid hormone receptor (TR).

93 the pituitary-specific transcription factor, Pit-1.

94 synergize with another transcription factor, Pit-1.

95 uce binding to the POU transcription factor, Pit-1.

96 P interacts with Pit-1 and is a cofactor for Pit-1-dependent activation of the human GH promoter.

97 e functions of CBP or p/CAF are required for Pit-1 function that is stimulated by cyclic AMP or growt

98 phobic beta-domain residues are required for Pit-1 isoform-specific repression of Ras signaling, and

99 hese findings are consistent with a role for Pit-1 as an initiating factor in hGH locus activation du

100 ue chromatin-mediated developmental role for Pit-1 in the hGH LCR.

101 from -53 to -19, whose pattern differed from Pit-1 in thyrotrope extracts, showed protection patterns

102 m via genes containing both POU homeodomain (Pit-1) and phorbol ester (AP-1) response elements.

103 ce between the promoter-proximal and the HSI Pit-1 binding sites can be attributed in part to a singl

104 ptake and phosphate-induced calcification in Pit-1 deficient cells.

105 ecular basis of disease-causing mutations in Pit-1 and provide potential basis for the flexible allos

106 Inactivating mutations in Pit-1 disrupt these processes, giving rise to the syndro

107 o show that two different point mutations in Pit-1, which disrupted distinct activities, affected the

108 vesicles, inhibition of phosphate uptake in Pit-1 knockdown cells blocked the induction of the osteo

109 sm with the TR without affecting independent Pit-1 activity were also identified.

110 selective activity and synergism-independent Pit-1 and TR functions.

111 heir effects on the much weaker, independent Pit-1 and TR activations of the rat growth hormone promo

112 ary cells that do not normally express Lhx3 (Pit-1/0 cells) were treated with 5-aza-2'-deoxycytidine,

113 Specifically, the putative monomeric Pit-1 binding site can be substituted with bona fide bin

114 Prior studies of the mouse Pit-1 (mPit-1) gene revealed that this master regulatory

115 in the upstream enhancer region of the mouse Pit-1 gene.

116 Activation of Pit-1 by cyclic AMP or growth factors depends on distinc

117 only a co-repressor complex, the activity of Pit-1 is determined by a regulated balance between a co-

118 Addition of Pit-1 increased Pitx2 binding to the bicoid element in e

119 This differential analysis of Pit-1/Pit-1beta isoform function provides significant in

120 POU-S domain is critical for the assembly of Pit-1 with C/EBPalpha, and they showed that DNA-binding

121 thermore, we demonstrate specific binding of Pit-1 to Pitx2 in vitro.

122 lusters containing different combinations of Pit-1-dependent cell types suggests that the Pit-1+ prec

123 We present evidence that expression of Pit-1 and limited commitment to these cells lineages occ

124 circuit that maintains durable expression of Pit-1 throughout adult life.

125 Pit-1 and ETS-1 and blocks the induction of Pit-1-dependent prolactin promoter activity by cAMP.

126 t the functional and physical interaction of Pit-1 and Ets-1 is mediated via the POU homeodomain, whi

127 Synergistic interaction of Pit-1 with a member of the Ets family of transcription f

128 Mutations of Pit-1 that selectively inhibited synergism with the TR w

129 Overexpression of Pit-1 restored phosphate uptake and phosphate-induced ca

130 us, the unique transcriptional properties of Pit-1 and Pit-1beta on the rPRL promoter may be due to t

131 main transcription factor, termed Prophet of Pit-1 (Prop-1).

132 The Prophet of Pit-1 (PROP1) gene encodes a paired class homeodomain tr

133 Prophet of Pit-1 (PROP1) is a homeodomain transcription factor esse

134 By using a series of Pit-1 internal-deletion constructs in a transient transf

135 the divergent bases between the two sets of Pit-1 elements results in a partial reversal of their tr

136 Treatment of Pit-1/0 pituitary cells with a combination of a demethyl

137 The allosteric effect on Pit-1, in combination with other DNA binding factors, re

138 AT) expression while HeLa cells require only Pit-1, a pituitary-specific factor.

139 A binding activity and is required for Pitx2-Pit-1 interaction and Pit-1 synergism.

140 activity was attributed primarily to POU1F1 (Pit-1) elements at HSI, as linkage to HSI was sufficient

141 ribe the endogenous TRbeta2 locus or produce Pit-1 protein, could be reconstituted to a level approac

142 inhibiting Lef-1 expression and may promote Pit-1 lineage differentiation during pituitary developme

143 en the pituitary-specific POU domain protein Pit-1 and members of the ETS transcription factor family

144 of transactivation by the POU domain protein Pit-1.

145 actions of the pituitary-specific HD protein Pit-1 control the development of anterior pituitary cell

146 the presence of the POU homeodomain protein Pit-1.

147 f the pituitary-specific POU domain protein, Pit-1.

148 on of Pitx2 and another homeodomain protein, Pit-1, yielded a synergistic 55-fold activation of the p

149 The more proximal Pit-1 sites, including the area from -53 to -19, whose p

150 he gibbon ape leukemia virus (GALV) receptor Pit-1 were used concurrently.

151 ghrelin/somatostatin/insulin/IGF-I-receptors/Pit-1).

152 s that abrogated binding of both recombinant Pit-1 and Pit-1-containing nuclear extracts revealed tha

153 that were indistinguishable from recombinant Pit-1.

154 ained sites that interacted with recombinant Pit-1; however, extracts of TtT-97 thyrotropes, which ex

155 ivation domains of both Pit-1 and TR reduced Pit-1/TR synergy in parallel with their effects on the m

156 itary development and that miR-26b regulates Pit-1 expression by inhibiting Lef-1 expression and may

157 Furthermore, miR-26b up-regulates Pit-1 and growth hormone expression by attenuating Lef-1

158 hat the Oct-1 POU domain but not the related Pit-1 POU domain can facilitate the binding of SNAPc to

159 ctivation by Pit-1 was dependent on the same Pit-1 sites shown to be important for basal TRbeta2 prom

160 A single Pit-1 DNA-binding element from the prolactin promoter is

161 ired for maintenance of expression) and that Pit-1-dependent activation of the distal enhancer can be

162 We have found that Pit-1 interacts with the distal portion of the P1 region

163 This analysis reveals that Pit-1 subdomains bind to perpendicular faces of the DNA,

164 We show that Pit-1 expression established a domain of histone hyperac

165 The Pit-1 gene remains continuously, highly expressed in the

166 Although the Pit-1 homeodomain is both necessary and sufficient for d

167 Because the Pit-1 sites in the hGH-N gene promoter are insufficient

168 ing autoregulatory mechanism mediated by the Pit-1 protein.

169 ealed that removal of regions containing the Pit-1 sites at -456 to -432, -149 to -127, and -124 to -

170 Consequently, we further defined the Pit-1 amino-terminal TAD into region 1 (R1, amino acids

171 s due to a mutation in the gene encoding the Pit-1 transcription factor.

172 nting identified protected G residues in the Pit-1, Sp1, and Zn-15 binding sites of the GH gene in GC

173 ing protein and Lhx3 promoter regions in the Pit-1/0 cell line.

174 However, T3 increased protection of the Pit-1 and Sp1 binding sites against DMS in GC cells.

175 findings suggest that the structures of the Pit-1 binding sites at HSI specify distinct chromatin-de

176 ss or synergy because block mutations of the Pit-1 interaction surface in Ets-1, which reduced Ets-1/

177 rent failure of initial determination of the Pit-1 lineage required for production of growth hormone,

178 Alternate splicing of the Pit-1 message produces the Pit-1beta isoform, which cont

179 port a high resolution X-ray analysis of the Pit-1 POU domain bound to a DNA element as a homodimer.

180 itary, consistent with the repression of the Pit-1 promoter by Lef-1.

181 This base affects the conformation of the Pit-1/DNA complex, and reciprocal exchange of the diverg

182 Lef-1 directly targets and represses the Pit-1 promoter.

183 genetic background, we demonstrate that the Pit-1 gene utilizes distinct enhancers for initial gene

184 e two transcriptional responses and that the Pit-1 R2 subregion represents a novel, tissue-specific R

185 Pit-1-dependent cell types suggests that the Pit-1+ precursor cells choose from multiple developmenta

186 esponding shifts in their proximities to the Pit-1 promoter.

187 Using the Pit-1-defective Snell dwarf as a genetic background, we

188 cal interaction of these two factors via the Pit-1 homeodomain (amino acids 199-291) and the Ets-1 re

189 These data support a model in which the Pit-1 binding sites in the hGH LCR allosterically progra

190 enrichment for H3K27 acetylation within the Pit-1 locus.

191 These Pit-1 elements are sufficient to activate hGH-N expressi

192 These Pit-1-dependent actions are accompanied by localized rec

193 present report we demonstrate that all three Pit-1 sites in the HSI array contribute to LCR activity

194 The presence of all three Pit-1-dependent cell types in clonally derived clusters

195 sults indicate that phosphate uptake through Pit-1 is essential for SMC calcification and phenotypic

196 Thus, Pit-1 and TR amplify each other's intrinsic activities.

197 o determine which type of Na/Pi transporter (Pit-1 or Pit-2) is regulated by PKC and which PKC isotyp

198 a sodium-dependent phosphate co-transporter, Pit-1 (Glvr-1).

199 as sodium-dependent phosphate transporters (Pit-1 and Pit-2, respectively).

200 Treated Pit-1/0 cells had decreased methylation at specific site

201 ining nuclear extracts revealed that the two Pit-1 sites between -149 and -102 were important for TRb

202 functionally distinct complexes of these two Pit-1 isoforms with Ets-1.

203 NA methylation levels, treated and untreated Pit-1/0 genomic DNAs were subjected to bisulfite convers

204 The identification of three in vitro Pit-1 binding sites within the HS-I region suggested a m

205 hypothesis directly and to determine whether Pit-1 expression is sufficient to confer hGH locus histo

206 n the HS-I region suggested a model in which Pit-1 binding at HS-I initiates the chromatin modificati

207 While Pit-1 appears necessary for TSH beta promoter activity i

208 These effects were coincident with Pit-1 occupancy at HS-I and the hGH-N promoter and were

209 xity for the interaction of ETS factors with Pit-1 target genes.

210 promoter (-133 to -88) region interacts with Pit-1 and an additional 50-kDa factor at an adjacent sit

211 We determined that CBP interacts with Pit-1 and is a cofactor for Pit-1-dependent activation o

212 we show that GATA-2 directly interacts with Pit-1 in solution.

213 S proteins revealed that ERF interferes with Pit-1 binding.

214 ressed the synergism of wild type PITX2 with Pit-1.

215 id not suppress the wild type synergism with Pit-1.

216 independently activate and to synergize with Pit-1 on pituitary-specific target gene promoters.

217 ity that appears to function in synergy with Pit-1, activators of A and C protein kinases and possibl

218 alian growth hormone promoter in tandem with Pit-1, was determined in order to elucidate the exon-int