ライフサイエンスコーパス: E2F4

1 ciated earlier with mutation of either Rb or E2f4.

2 oters were bound by E2F6, but not by E2F1 or E2F4.

3 ted with increased cytosolic localization of E2F4.

4 ranscriptionally regulated, in part, by p130:E2F4.

5 ction of the C-terminal Rb binding region of E2F4.

6 n B1 and decreased levels of CDK2, CDK4, and E2F4.

7 E2F1 and was not observed in E2F2, E2F3, or E2F4.

8 p130 and the inhibitory transcription factor E2F4.

9 sence of either E2F2 or E2F3 but not E2F1 or E2F4.

10 o role of the predominant E2F family member, E2F4.

11 amatic increase in the level of E2F1 but not E2F4.

12 es are observed: cdk2/E2F/p107, E2F/p130 and E2F4.

13 ic translocation of the transcription factor E2f4.

14 onstrated that Trim28 can bind both E2F3 and E2F4.

15 the cytoplasmic-to-nuclear translocation of E2F4.

16 ir-17, suggestive of regulation of miRNAs by E2F4.

17 effect was blocked by a cDNA expressing the E2F4 3'-UTR sense strand.

18 that both beta-catenin and TCF4 bind to the E2F4 3'-UTR site in vivo, inducing expression of an E2F4

19 as growth-restraining members of the family (E2F4, -5, and -6) have little effect.

20 containing Smad3, the transcription factors E2F4/5 and DP1, and the corepressor p107 preexists in th

21 timate recipients of cdk regulatory signals, E2F4/5 and p107 act here as transducers of TGFbeta recep

22 cence through scaffolding MuvB proteins with E2F4/5 and the Rb tumor suppressor paralog p107 or p130.

23 As E2F4/5 are essential downstream mediators for a p16INK4a

24 sting of a Smad-binding site and an adjacent E2F4/5 element, structurally similar to the TIE found on

25 1 also blocks the function of E2F4 and E2F5 (E2F4/5) transcription factors through promoting their nu

26 of TGF-beta by forming a complex with Smad3, E2F4/5, and p107 at the TGF-beta inhibitory element (TIE

27 occupancy of ER-alpha promoter by pRb2/p130-E2F4/5-HDAC1-SUV39 H1-p300 and pRb2/p130-E2F4/5-HDAC1-SU

28 130-E2F4/5-HDAC1-SUV39 H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 complexes, and provided a lin

29 tion of transcription at G1/S and a role for E2F4-8 in repressing the same group of E2F1-3 target gen

30 quired for Schwann cell differentiation, and E2F4, a cell cycle regulator, showed a strong requiremen

31 dition to its effects on cell proliferation, E2F4 actively promotes the neuronal differentiation of P

32 ese observations suggest a critical role for E2F4 activity in controlling the maturation of cells in

33 To study the effect of deregulated E2F4 activity on cell growth control and tumorigenesis,

34 We have generated mice deficient in E2F4 activity, the major form of E2F in many cell types.

35 y and its binding partner DP-1 revealed that E2F4 acts as an activator as well as a repressor.

36 In this study, we analyse how loss of E2f4 affects the tumorigenicity of pRB-deficient tissues

37 This analysis shows that loss of E2F4 allows cells to undergo spontaneous differentiation

38 We focused on whether E2F4, an E2F member believed to exhibit crucial control

39 Further characterization of the role of E2F4 and Daxx as well as other differentially expressed

40 E2F4 and DP2 interact through an extensive protein-prote

41 strate that LMP1 also blocks the function of E2F4 and E2F5 (E2F4/5) transcription factors through pro

42 Thus, E2F4 and E2F5 are dispensable for cell cycle progression

43 E2F4 and E2F5 constitute a defined subset of the family.

44 ly reflects the control of expression of the E2F4 and E2F5 genes.

45 we report that simultaneous inactivation of E2F4 and E2F5 in mice results in neonatal lethality, sug

46 g a supershift with the antibody against the E2F4 and E2F5 pocket protein, p107.

47 But, unlike the E2F4 and E2F5 proteins, which are also expressed in quie

48 7 and p130 almost exclusively associate with E2F4 and E2F5.

49 Indeed, inhibition of both E2F4 and E2F6 activity results in specific derepression

50 ate corepressor complexes consisting of p130-E2F4 and HDAC1/2-mSin3B from the promoters of E2F-regula

51 ysis provided evidence of versatile roles of E2F4 and insights into its functions.

52 trated that both the nuclear localization of E2F4 and its association with the Rb family member p130

53 Overexpression of E2F4 and its transcriptional cofactors of the retinoblas

54 s involves the DREAM complex (DP, p130/RBL2, E2F4 and MuvB), a newly identified key regulator of quie

55 ining p107 and enhances its interaction with E2F4 and other p107 partners.

56 )/early G(1), Mip/LIN-9 forms a complex with E2F4 and p107 or p130, while in late G(1)/S phase, it as

57 F4/p130 complexes and increased occupancy of E2F4 and p130 at the RAD51 and BRCA1 promoters.

58 t bound an inhibitory E2F complex containing E2F4 and p130.

59 Loss of E-cadherin activates the E2F4 and p130/107 transcription repressor complexes to s

60 We find that E2F4 and pocket protein association with the Plk1 promot

61 gulation of pocket protein interactions with E2F4 and the expression of p107 and E2F1, both E2F-regul

62 cell cycle regulatory transcription factors E2F4 and the MAGE protein necdin were similarly altered

63 growth and may involve interactions between E2F4 and the neuronal differentiation program itself.

64 lex, together with the Rb-like protein p130, E2F4, and DP1, forms the DREAM complex during quiescence

65 minimally affects the binding of E2F2, E2F3, E2F4, and E2F5 but significantly inhibits the binding of

66 t the C-terminal activation domains of E2F1, E2F4, and E2F5, when fused to the Gal4 DNA binding domai

67 We determined that most E2F1, E2F4, and E2F6 binding sites are located within 2 kb of

68 Second, it is a specific property of E2F4, and not other E2Fs, and it occurs independently of

69 F-beta increases the nuclear localization of E2F4, and presumably the transcriptional repression of t

70 ner for repression of pro-apoptotic genes is E2F4, and that the p130-E2F4 complex recruits the chroma

71 onal suppression involving Smads 2 and 3, Rb/E2F4, and the cell-cycle repressor elements CDE and CHR.

72 nding activity, composed largely of E2F2 and E2F4, and the growth-suppressive E2F4-p130 complexes.

73 nt signaling, also induced expression of the E2F4 antisense transcript and decreased E2F4 protein lev

74 -UTR site in vivo, inducing expression of an E2F4 antisense transcript.

75 egulated the in vivo transition from E2F3 to E2F4 as the major E2F DNA binding activity, and its cont

76 ase in E2F4 protein was reflected by reduced E2F4 association with specific target genes, including C

77 are lost rapidly along with the presence of E2F4 at E2F-containing B-Myb promoter sites.

78 Chromatin immunoprecipitation localized E2F4 at promoter regions of the Bub3 and Pttg1 mitotic g

79 The switch between E2F1 and E2F4 at the E2F binding site of the cyclin B1 promoter c

80 the occupancy of the transcription repressor E2F4 at the EZH2 promoter following PARP inhibition.

81 reduced expression of E2F1 and E2F2, but not E2F4, at the mRNA and protein levels.

82 regulated by Sp1 and negatively regulated by E2F4-based transcriptional complexes.

83 data suggest that in response to radiation, E2F4 becomes active in the nucleus, enforces a stable G(

84 While half of all E2F4 binding sites (56%) occurred near transcription sta

85 E2F4 binding sites also occurred near regulatory element

86 uencing (ChIP-seq) to identify around 16,000 E2F4 binding sites which potentially regulate 7346 downs

87 was accompanied by decreased p130, p107, and E2F4 binding to Cdk2.

88 ncrease of E2F4 levels led to an increase in E2F4 binding to p130 but had no effect on E2F4/p107 or E

89 cting E2F site in the cdc2 promoter, whereas E2F4 binds to the negative-acting site.

90 ound to the activator site and both E2F1 and E2F4 bound to the repressor site of the Rb promoter in v

91 ate that BRG1 binds specifically to E2F6 and E2F4 but not the activator E2Fs.

92 Individual export mutants of E2F4, but not a mutant with inactivation of both export

93 ssed in keratinocytes transgenic for E2F1 or E2F4, but not in c-myc transgenics.

94 bunit protein complex that contains p130 and E2F4, but not pRB, and mediates the repression of cell c

95 r, inactivation of Rb or substitution of the E2F4 C-terminal domain by the E2F1 C-terminal region res

96 In the absence of E2F6, E2F4 can bind to the G1/S-regulated promoters and compen

97 experiments we determined that E2F1, but not E2F4, can strongly transactivate the human p21 gene thro

98 er, other members of the E2F family (such as E2F4) cannot.

99 carcinogenesis by reducing the level of the E2F4 cell cycle repressor via an antisense mechanism.

100 Moreover, a subset of the Rb(-/-);E2f4(-/-) chimeras developed either low- or high-grade c

101 ssion increased the longevity of the Rb(-/-);E2f4(-/-) chimeric animals allowing us to identify novel

102 line mice die in utero, we generated Rb(-/-);E2f4(-/-) chimeric animals to allow examination of adult

103 Following radiation treatment, E2F4 colocalized with p130 in the nucleus during a radia

104 through small interfering RNA prevented p130/E2F4 complex formation and sensitized cells to IR-induce

105 The C/EBPalpha-Rb-E2F4 complex occupies the c-myc promoter and blocks indu

106 o-apoptotic genes is E2F4, and that the p130-E2F4 complex recruits the chromatin modifiers HDAC1 and

107 We identified an age-specific C/EBPalpha-Rb-E2F4 complex that binds to E2F-dependent promoters and r

108 y the transcriptional repression of the p130:E2F4 complex.

109 xpression and a shift to an active repressor E2F4 complex.

110 roteins and the release of p130 and pRB from E2F4 complexes allows formation of E2F1 complexes not on

111 mal growth-arrested enterocytes contain p130-E2F4 complexes and that T-antigen expression destroys th

112 in response to either p53 or p21 induction, E2F4 complexes are specifically recruited onto the promo

113 not with p53 activation targets, implicating E2F4 complexes as effectors of p21-dependent p53-mediate

114 nally, amounts of p27-cyclin E and RB-2/p130-E2F4 complexes were found to increase in CA-OV3 cells gr

115 30 and p107 as well as the formation of p107-E2F4 complexes.

116 lation in the nucleus, and formation of RBL2/E2F4 complexes.

117 Taken together, our data show that pRB and E2F4 cooperate in placental development, but play largel

118 We found that p130 and E2F4 cooperatively repress a common set of genes under e

119 We analyzed the impact of E2F4 deficiency on early steps in mouse hematopoietic de

120 Here we establish that E2f4 deficiency reduced the lifespan of Rb(-/-) embryos

121 Here we show that E2f4-deficiency leads to an absence of ciliated cells fr

122 The E2F4-deficient progenitor cells showed reduced expressio

123 type p53-mediated inhibition of UBE2C is p21-E2F4-dependent and GOF mutant p53-mediated transactivati

124 y the cyclin kinase inhibitor p16(INK4a), an E2F4-dependent process.

125 4A) pulse, abolishing the shift from E2F3 to E2F4, derepressing E2F target genes, and expanding a ste

126 nizing centres and that, without cytoplasmic E2f4, deuterosomes are not assembled, halting multicilio

127 Trim28 depletion increased E2F3 and E2F4 DNA binding activity, as measured by chromatin-immu

128 006474 resulted in the loss of intracellular E2F4 DNA-binding activity as measured by electrophoretic

129 Unlike E2F1, E2F4 does not induce apoptosis, and this correlates with

130 vator E2F1 to complexes containing repressor E2F4, downregulating BRCA1 expression.

131 DREAM contains p130, E2F4, DP1, and a stable core complex of five MuvB-like p

132 enetically repressing XPC and inhibiting the E2F4/DP1 complex.

133 The crystal structure of an E2F4-DP2-DNA complex shows that the DNA-binding domains

134 the known crystal structure of the DNA-bound E2F4/DP2 heterodimer.

135 hat the ability of HDAC1 to repress E2F3 and E2F4-driven transcription is dependent on Trim28.

136 es, two other kinases, transcription factors E2F4, E2F5, and p130, a DNA repair gene, a gene for the

137 E2F1, E2F2, and E2F3a) or repressors (E2F3b, E2F4, E2F5, E2F6, and E2F7).

138 Downstream E2F4/E2F5 targets, which are potentially involved in the

139 l of cell cycle transcription factors (E2F1, E2F4, E2F6, and GABPA) from the Encyclopedia of DNA Elem

140 These Rb(-/-);E2f4(-/-) embryos exhibited all of the defects character

141 d a conditional mouse model to allow Rb(-/-);E2f4(-/-) embryos to develop in the presence of Rb wild-

142 E2F4 export is mediated by two hydrophobic export sequen

143 hese data suggest that changes in necdin and E2F4 expression after rosiglitazone exposure in humans a

144 E2F4 expression was decreased by 10-fold in muscle and 2

145 Finally, E2F4 expression was found to increase dramatically in th

146 Further, the downregulation of E2F4 expression with antisense oligodeoxynucleotides inh

147 RBL2/E2F4 formation in turn led to a shift in BRCA1 promoter

148 scriptional program of centriole biogenesis, E2f4 forms apical cytoplasmic organizing centres for ass

149 lear export contributes to the regulation of E2F4 function, including its ability to regulate exit fr

150 nally differentiated cells, common KDM5A and E2F4 gene targets were bound by the pRB-related protein

151 nesis, transgenic mouse lines expressing the E2F4 gene under the control of a keratin 5 (K5) promoter

152 o the 3'-untranslated region (3'-UTR) of the E2F4 gene.

153 t inducer of apoptosis whereas its relative, E2F4, generally does not promote cell death.

154 As Rb(-/-);E2f4(-/-) germline mice die in utero, we generated Rb(-/

155 We found that loss of E2f4 had a differential effect on known Rb-associated ne

156 Remarkably, loss of E2F4 had no detectable effect on either cell cycle arres

157 cription start site regions independently of E2F4; however, it cooperated with E2F4 to promote a stat

158 These findings emphasize the significance of E2F4 in controlling gene expression and cell fate.

159 ed by interplay between Sp1, p107, p130, and E2F4 in distinct transcriptional complexes during skelet

160 on heterologous promoters and binds to p130/E2F4 in response to overexpression of p53.

161 he -401 TIE was capable of binding Samd3 and E2F4 in TGFbeta-treated cells.

162 ket protein is required to act downstream of E2F4 in the differentiation process.

163 We investigated the role of E2F4 in the genotoxic stress response.

164 To examine the role of E2F4 in tumor development, the mouse skin two-stage carc

165 RB family/E2F complexes, which includes p130/E2F4, in response to genotoxic agents, is not well under

166 sociated with an amino-terminal extension of E2F4, in which an arginine binds in the minor groove nea

167 on of VSMCs leading to increased IH, whereas E2F4 inhibits this pathological response.

168 Thus, E2f4 integrates nuclear and previously unsuspected cytop

169 ether, these findings show that p130 escorts E2F4 into the nucleus and, together with corepressor com

170 We have found that E2F4 is actively exported from the nucleus and that lept

171 E2F4 is an E2F family member that has been proposed to b

172 Here, we demonstrate that E2F4 is highly upregulated following the neuronal differ

173 This suggests that E2F4 is important in early stages of commitment to the l

174 The separation of Mip/LIN-9 from p107,p130/E2F4 is likely driven by phosphorylation of the pocket p

175 ree E2F DNA binding activity is reduced, and E2F4 is primarily nuclear.

176 We therefore conclude that E2f4 is required to determine the appropriate developmen

177 E2F4 is the major pRB-associated E2F in vivo, yet its ro

178 E2F4 is the most abundant E2F protein in many cell types

179 In contrast, E2F4 is unable to bind to the -143/+10 region of the Mcl

180 We propose that E2F4 is unable to repress the Mcl-1 promoter primarily a

181 rom the binding site by AR and replaced with E2F4, leading to the recruitment of the silencing mediat

182 The IR-induced increase of E2F4 levels led to an increase in E2F4 binding to p130 b

183 In addition, in the proximal lung, E2f4 loss causes a reduction in Clara cell marker expres

184 t striking effect was in the pituitary where E2F4 loss delayed the development, and reduced the incid

185 In addition, E2F4 loss does not override the differentiation defect r

186 This suggests that E2F4 makes a major contribution to the control of erythr

187 The forced expression of E2F4 markedly enhanced the rate of PC12 cell differentia

188 E2F4 may be an important participant in the terminal dif

189 showed histone modifications suggesting that E2F4 may function as a long-range regulator, which we co

190 E2f4-/- mice died of an increased susceptibility to oppo

191 icularly striking in the nasal epithelium of E2f4-/- mice where ciliated cells are replaced by column

192 lite repeats in the TGFbetaIIR, IGFIIR, BAX, E2F4, MSH3, MSH6, BRCA1, and BRCA2 genes were generally

193 tions that causes the postnatal lethality of E2f4 mutant mice.

194 f trophectoderm-like cells in both Rb and Rb;E2f4 mutant placentas.

195 Using genetically altered mice and E2F4 mutant proteins we demonstrate that centriole ampli

196 Under these conditions, Rb(-/-);E2f4(-/-) mutants survived to birth.

197 ic binding to DNA of the c-Fos, c-Jun, E2F1, E2F4, MyoD, myogenin, and c-Myc transcription factors.

198 factors including c-Fos, c-Jun, AP-2, E2F1, E2F4, NF-kappaB, MyoD, and myogenin.

199 l set of motifs, including GABPA, MYC, E2F1, E2F4, NRF-1, CCAAT, YY1, and ACTACAnnTCC are overreprese

200 p130 deficiency triggered a dramatic loss of E2F4 nuclear localization as well as transcriptional der

201 E2F4-null mouse embryonic fibroblasts were less sensitiv

202 E2F4 occupies promoter regions of proapoptotic factors,

203 monstrate that while the effects of E2F1 and E2F4 on cell proliferation in vivo are similar, their ap

204 d p130 formed transcriptional complexes with E2F4 on the FGFR1 promoter and repressed FGFR1 gene tran

205 mediated through switching between E2F1 and E2F4 on the promoter of cyclin B1.

206 al recruitment of E2F3 by EWS-FLI1 replacing E2F4 on their target promoters.

207 and phosphorylates E2F1, -2, and -3 (but not E2F4 or -5) and the RB-related pocket proteins p130 and

208 does not affect its ability to interact with E2F4 or cyclins.

209 cilin acts by forming a ternary complex with E2f4 or E2f5 and Dp1 that binds and activates most of th

210 Interaction between NS1 and E2F4 or E2F5 enhanced the nuclear import of these repres

211 adipocytes with rosiglitazone did not alter E2F4 or necdin, expression of both genes was significant

212 ath while interference with the synthesis of E2F4 or p130, or with the interaction of E2F4-p130 with

213 posttranscriptional increase in the level of E2F4, p105(Rb), and p130 and induced the formation of nu

214 g the replacement of free E2F complexes with E2F4-p105(Rb) complexes.

215 duced the formation of nuclear E2F4-p130 and E2F4-p105(Rb) complexes.

216 directly regulated by unique combinations of E2F4, p107, and p130, including a group of genes specifi

217 s define a specific function for E2F4-RB and E2F4-p107 complexes in gene repression under TGF-beta tr

218 T cells induced the formation of E2F4-RB and E2F4-p107 complexes, which are capable of binding to E2F

219 emonstrated that Sp1 interacted with p107 in E2F4-p107 transcriptional complexes in myoblasts.

220 ed muscle fibers by the relative loss of the E2F4-p107-Sp1 transcription complex and replacement by t

221 in E2F4 binding to p130 but had no effect on E2F4/p107 or E2F5/p130 complexes.

222 The E2F4/p107/cyclin E/CDK2 complex, a minor component in pr

223 nd p130 and induced the formation of nuclear E2F4-p130 and E2F4-p105(Rb) complexes.

224 E2F4-p130 becomes the predominant E2F-pocket complex for

225 ion complex and replacement by the repressor E2F4-p130 complex.

226 Following stress exposure, E2F4-p130 complexes are lost rapidly along with the pres

227 man keratinocytes includes the generation of E2F4-p130 complexes that in association with histone dea

228 vity, dissociation of cyclin A-CDK2 from the E2F4-p130 complexes, and inhibition of G(1)/S transition

229 of E2F2 and E2F4, and the growth-suppressive E2F4-p130 complexes.

230 of E2F4 or p130, or with the interaction of E2F4-p130 with chromatin modifiers, induces neuron death

231 and death are dependent on the integrity of E2F4-p130-HDAC/Suv39H1 complexes.

232 Following mitogenic stimulation, repressive E2F4-p130-histone deacetylase complexes dissociate from,

233 The increase in E2F4/p130 association after IR was observed in prostate

234 E2F4/p130 complex formation was dependent on dissociatio

235 ar accumulation, leading to the formation of E2F4/p130 complexes and increased occupancy of E2F4 and

236 3/pRB by constitutively expressed repressive E2F4/p130 complexes on target genes upon EWS-FLI1 modula

237 poxia is specifically mediated by repressive E2F4/p130 complexes that bind to a single E2F site in th

238 gram mediated by the formation of repressive E2F4/p130 complexes that represents an integral response

239 the BRCA1 and RAD51 promoters by repressive E2F4/p130 complexes, a pathway prevented by expression o

240 n, as was the cdk4-dependent dissociation of E2F4/p130 complexes.

241 at the transcriptional level via repressive E2F4/p130 complexes.

242 The E2F4/p130 pocket protein complex emerges as a new target

243 Thus, Rb and E2f4 play cooperative roles in placental development.

244 to E2F1 and E2F3, which sensitize to death, E2F4 plays a crucial protective role in neuronal death e

245 Taken together, we propose a model by which E2F4 plays a protective role in neurons from ischemic in

246 mplex, whose key components include p130 and E2F4, plays a fundamental role in repression of cell cyc

247 Finally, our results indicate that E2F4 promoter occupancy is globally associated with p53-

248 M006474 resulted in down-regulation of total E2F4 protein as well as known E2F targets.

249 The E2F4 protein is involved in gene repression and cell cyc

250 E2F4 protein levels increased and accumulated in the nuc

251 the E2F4 antisense transcript and decreased E2F4 protein levels.

252 The antisense-mediated decrease in E2F4 protein was reflected by reduced E2F4 association w

253 These results define a specific function for E2F4-RB and E2F4-p107 complexes in gene repression under

254 ment of HaCaT cells induced the formation of E2F4-RB and E2F4-p107 complexes, which are capable of bi

255 essor pathway and the assembly of repressing E2F4-Rb DNA binding complexes.

256 p130 "form 3," which does not interact with E2F4, readily interacts with E2F1.

257 Moreover, abrogation of E2F4 recruitment via the inactivation of RB pocket prote

258 Rb and the subsequent association of the Rb/E2F4 repressive complex to CDE/CHR elements in the proxi

259 o E2F promoters where it eliminates p130 and E2F4, resulting in the dramatic elimination of H3 Lys-9

260 Analysis of newborn pups deficient in E2F4 revealed abnormalities in hematopoietic lineage dev

261 t other E2Fs, and it occurs independently of E2F4's ability to interact with pocket proteins.

262 terference RNA (siRNA)-mediated knockdown of E2F4 sensitized cells to subsequent irradiation, resulti

263 and increased phosphorylation and decreased E2F4 sequestering ability of the CDK4 target, p130/Rb2.

264 of the defects characteristic of the Rb and E2f4 single mutants and had no novel defects.

265 resses Brca1 transcription by binding to the E2F4 site of the Brca1 promoter.

266 0 hyperphosphorylation, dissociation of p130-E2F4-Suv39H1-HDAC complexes, altered modification of H3

267 rt of a Sin3 complex and that on a subset of E2F4 target genes, the coordinated activity of Sin3 and

268 d to permanent gene silencing on a subset of E2F4 target genes.

269 Downstream E2F4 targets potentially involved in the progression fro

270 inding targets of human transcription factor E2F4 that we independently validated by promoter-specifi

271 E2F4, the most abundant E2F protein, is thought to act i

272 Disruption of E2F4 through small interfering RNA prevented p130/E2F4 c

273 1) with the p130 or p107 pocket proteins and E2F4 to a transcriptionally active complex in S-G(2) con

274 oblastoma protein p130/Rb2, which sequesters E2F4 to block entry into G1, 10-fold elevated levels of

275 to E2F3a) and upregulating repressive E2Fs (E2F4 to E2F8) in the primary CD36(+) EPCs.

276 The ability of E2F4 to prevent adipogenesis seems to be quite distinct

277 ndently of E2F4; however, it cooperated with E2F4 to promote a state of deepened repression at cell c

278 onally, we detected binding of both E2F1 and E2F4 to the Rb promoter in vivo using chromatin immunopr

279 lls, free E2F DNA binding activity (E2F2 and E2F4, to a lesser extent E2F1, E2F3, and occasionally E2

280 lation of residues S650 and S975 weakens the E2F4 transactivation domain binding.

281 nct residues regulates p107 affinity for the E2F4 transactivation domain.

282 ian cells in culture, to dissociate the p130-E2F4 transcription factor complex, and to stimulate ATP

283 that the promoters of 127 were bound by the E2F4 transcription factor in primary fibroblasts.

284 substantial portion of target genes with the E2F4 transcription factor.

285 Furthermore, expression of E2F1, but not E2F4, transcription factor in mouse fibroblasts represse

286 Unlike E2F1 transgenic mice, E2F4 transgenic mice developed skin tumors with a decrea

287 E2F4 was always nuclear in limbal epithelium and cytopla

288 However, E2F4 was essential for normal development.

289 een observed in vitro, ectopically expressed E2F4 was found to localize to the nucleus and induce pro

290 omoter activity, repression by E2F1, but not E2F4, was enhanced by the coexpression of pRB.

291 atin immunoprecipitated using an antibody to E2F4, we have identified 68 unique target loci; 15% are

292 owed that expression of cyclin D1, CDK2, and E2F4 were increased, and Rb levels were decreased in the

293 Some genes (e.g., E2F4) were overexpressed in tumor epithelial cells and s

294 ted the transcriptional activity of E2F3 and E2F4, whereas Trim28 deficiency enhanced their activity.

295 This contrasts with the effects of E2F4, which enhances the differentiation state of PC12 c

296 ctions, involving all E2F species, including E2F4, which is paralleled by the conversion of Rb from a

297 bpalpha, which enforces differentiation, and E2F4, which suppresses cell-cycle re-entry.

298 activity, enhancing the binding of p130 and E2F4, which together bind to and repress the cdc2 promot

299 for its ability to reduce the association of E2F4 with p107 and p130.

300 oscopy indicated co-localization of E2F3 and E2F4 with Trim28 within the cell nucleus, and co-immunop