ライフサイエンスコーパス: TAL1

1 transcription factor stem cell leukemia (SCL/Tal1).

2 role of T-cell acute lymphocytic leukemia 1 (TAL1).

3 GATA2) and erythro-megakaryocytic (GATA2 and TAL1).

4 en combined with overexpression of GATA-4 or TAL1.

5 Sirt1 playing a role upstream of GATA-4 and TAL1.

6 nt of those regulated by the GATA factors or TAL1.

7 ss wild-type Tal1 or a DNA-binding mutant of TAL1.

8 ents were occupied by neither GATA-2 nor Scl/TAL1.

9 4,000 locations were bound by both GATA1 and TAL1.

10 cells that express the transcription factor TAL1.

11 three transcription factors: GATA1, FLI1 and TAL1.

12 pisomal reintegration in a single site 5' to TAL1.

13 ey transcription factors including GATA1 and TAL1.

14 responses to three TALs expressed in worms (TAL1, -3, and -5) became more prevalent with age.

15 gene regulation of the transcription factor TAL1, a critical regulator of hematopoiesis, at multiple

16 previously unaligned reads corresponding to TAL1, a human TF involved in lineage specification of he

17 sing knockout mice, we study the function of Tal1, a key haematopoietic transcription factor, and dem

18 SCL/TAL1, a tissue-specific transcription factor of the basi

19 d that erythroid master regulators GATA1 and TAL1 act cooperatively within active enhancers but confe

20 mechanistic diversity, the mode of oncogenic TAL1 activation, rather than expression levels, impact o

21 Dysregulation of TAL1 activity has been associated with T-cell leukemogen

22 ating endocardial extension, suggesting that Tal1 activity influences the behavior of individual endo

23 tream effector of NOTCH1, and preventing SCL/TAL1 activity.

24 Here, we show that the transcription factor TAL1 (also known as SCL) binds to the promoter of the NF

25 we demonstrate that the transcription factor Tal1 (also known as Scl) is indispensable for the establ

26 tical factors that are directly activated by TAL1 and contribute to T-ALL pathogenesis are largely un

27 remains unclear how the interactions between TAL1 and corepressors versus co-activators are properly

28 TRIB2 gene, which is oppositely regulated by TAL1 and E2A/HEB and is essential for the survival of T-

29 ion analysis demonstrated the association of Tal1 and E47, one of its E protein DNA-binding partners,

30 ding the basic helix-loop-helix proteins SCL/TAL1 and E47, the zinc finger protein GATA-1, and LIM-do

31 o erythropoietin with concomitantly elevated TAL1 and EPO-R expression.

32 A link between elevated TAL1 and excessive erythrocytosis is suggested by erythr

33 l alterations in the binding patterns of SCL/TAL1 and FLI1.

34 plex that contains the transcription factors Tal1 and GATA-1, the LIM domain protein Lmo2, and Ldb1 a

35 We show that TAL1 and GATA1 form a precisely organized complex at a c

36 Both TAL1 and GATA1 generated distinct characteristic ChIP-ex

37 LR, Fcgamma and SIGLEC receptors, as well as TAL1 and IFI16, regulators of proliferation and cell cyc

38 id-important transcription factors Gata1 and Tal1 and is essential for terminal erythropoiesis.

39 ified the miRNA genes directly controlled by TAL1 and its regulatory partners HEB, E2A, LMO1/2, GATA3

40 scriptional regulatory circuit controlled by TAL1 and its regulatory partners HEB, E2A, LMO1/2, GATA3

41 RID5B positively regulates the expression of TAL1 and its regulatory partners.

42 pre-LSCs, which were induced here by the SCL/TAL1 and LMO1 oncogenes.

43 /LDB1 complex is observed in human T-ALL and Tal1 and Lmo2 expression in mice results in disease acce

44 Thymic expression of the Tal1 and Lmo2 oncogenes in mice results in rapid develop

45 These findings redefine how TAL1 and neighboring genes communicate within the nucleu

46 fically, we identify UTX as a coactivator of TAL1 and show that it acts as a major regulator of the T

47 d, intriguingly, loops occurring between the TAL1 and STIL genes at the common TAL1/STIL breakpoints

48 ion of GATA-4 and the basic helix-loop-helix TAL1 and that knockdown of both factors promotes differe

49 emia (T-ALL), often due to deletions between TAL1 and the neighboring STIL gene.

50 derexpression of leukemia-associated (MLLT3, TAL1) and erythropoiesis-associated (GATA3, EPOR, ANK1,

51 Runx1, Scl (Tal1) and Hhex expression is upregulated within 3 hours

52 Numerous TFs, including Scl (Tal1) and PU.1 (Spi1), are known regulators of developme

53 regulators of hematopoiesis (GATA-1 and Scl/TAL1) and the non-DNA binding components ETO2, the LIM d

54 of the endothelium is known to require SCL (TAL1), and an SCL-E12 (SCL-Tcfe2a) heterodimer can bind

55 T cell acute lymphocytic leukemia 1 protein (Tal1), and Erythroid Kruppel-like factor (EKLF; hencefor

56 tose phosphate pathway enzyme transaldolase (TAL1), and the transcription factor vitamin H response t

57 poietic transcription factors (GATA1, GATA2, TAL1, and FLI1) and three diagnostic histone modificatio

58 A-binding complex containing LMO2, LDB1, SCL/TAL1, and GATA-1.

59 m of cloche and the transcription factor Scl/Tal1, and is maintained by Hedgehog and vascular endothe

60 ineage-specific transcription factors Gata1, Tal1, and Klf1.

61 ing strong functional synergy between Gata1, Tal1, and Klf1.

62 TA1-occupied segments that are also bound by TAL1, and show evolutionary constraint on the GATA1-bind

63 These data suggest that GATA-4, TAL1, and Sirt1 cross-talk each other to regulate myogen

64 alters the expression of a crucial subset of TAL1- and NOTCH1-regulated genes, including the MYB and

65 and GATA-2 function combinatorially with Scl/TAL1, another key regulator of hematopoiesis.

66 How GATA1 and TAL1 are juxtaposed along the DNA and their cognate DNA

67 Genes flanking TAL1 are partly dependent on hub integrity for their tra

68 entified binding of the transcription factor TAL1 as a potential mediator of the increased expression

69 ith the dual roles of TAL1 in transcription, TAL1-associated LSD1 is decreased while recruitment of h

70 Furthermore, we demonstrate that the TAL1-associated LSD1, HDAC1, and their enzymatic activit

71 n and suggest that the dynamic regulation of TAL1-associated LSD1/HDAC1 complex may determine the ons

72 ic phenotype in Jurkat cells and showed that TAL1 binding can be associated with either repression or

73 tors appears to be a stronger determinant of TAL1 binding to chromatin than the canonical E-box bindi

74 These data suggest that TAL1 binds to the EPO-R promoter to activate EPO-R expre

75 ining the EPO-R transcription start site and TAL1 binds to the flanking 5' GATA and 3' E-box regions

76 shifting has been demonstrated to facilitate TAL1 but not GATA-1 binding to regulate target gene expr

77 shifting specifically facilitates binding of TAL1 but not GATA1 and is linked to subsequent transcrip

78 Finally, wild-type Tal1, but not a DNA binding-defective mutant, rescued th

79 Gata1 and Tal1 can assemble within higher-order protein complexes

80 This represents first in vivo evidence that Tal1 can completely inhibit E47/E2A function.

81 Yet, over half of the TAL1(+) cases lack TAL1 lesions, suggesting unrecognized

82 ings into close physical proximity all known TAL1 cis-regulatory elements including CTCF-bound insula

83 atory loop with GATA3 and RUNX1 and that the TAL1 complex directly activates the MYB oncogene, formin

84 ormal thymocytes, while it is induced by the TAL1 complex in human T-ALL cells.

85 the same amino acid can selectively inhibit TAL1 complex or FOG1 binding, producing distinct cellula

86 Diminished TAL1 complex recruitment mainly impairs transcriptional

87 loci encoding multiple components of the Scl/TAL1 complex, a master regulator of hematopoiesis and le

88 ather, one of these disrupted binding to the TAL1 complex, implicating it in diseases caused by GATA1

89 ound at its promoter and up-regulated by the TAL1 complex.

90 Scl/Tal1 confers hemogenic competence and prevents ectopic c

91 y erythroid transcription factors, GATA1 and TAL1, cooperate, along with other proteins, to regulate

92 Consistent with the rapid changes of TAL1-corepressor complex during differentiation, TAL1 re

93 The defects in endocardial behavior in tal1-deficient embryos originate during the earliest ste

94 earliest steps of endocardial morphogenesis: tal1-deficient endocardial cells fail to generate a cohe

95 r time, a progressively increasing number of tal1-deficient endocardial cells initiate myocardial gen

96 In addition, we find that the tal1-deficient endocardium fails to maintain its identit

97 junction protein ZO-1 is mislocalized in the tal1-deficient endocardium, indicating a defect in inter

98 of ectopic myocardial gene expression in the tal1-deficient endocardium.

99 The sequence responsible for Tal1 degradation was localized to a region in the C term

100 biquitination and degradation, CHIP promoted Tal1 degradation with both chaperone binding and ubiquit

101 own double- or single-E-box binding factors (TAL1, deltaEF1, E2A, HEB, etc.) failed to identify this

102 egulated T-ALL, and PIK3R1/PTEN mutations in TAL1 deregulated ALL, which suggests that different sign

103 D1 plays an important role in repressing the TAL1-directed transcription of GAL4 reporter linked to a

104 The GATA1 coregulators FOG1 and TAL1 dissociate from mitotic chromatin, suggesting that

105 gly, mice expressing a DNA-binding mutant of Tal1 do not exhibit increases in S phase cells.

106 ighly sensitive to BCL-2 inhibition, whereas TAL1 driven tumors mostly showed poor ABT-199 responses.

107 ivation of genes whose promoters occupied by TAL1, E2A, and HEB.

108 I bHLH proteins E2A and HEB, suggesting that TAL1/E2A as well as TAL1/HEB heterodimers play a role in

109 transcriptional complex consisting of LMO2, TAL1, E47, GATA1 and LDB1 that recognizes bipartite E-bo

110 Similarly, a TAL1/E47/LMO2/LDB1 complex is observed in human T-ALL an

111 tube formation: in zebrafish embryos lacking Tal1, endocardial cells form a disorganized mass within

112 ression signatures involving TAL1 targets in TAL1-expressing compared with -nonexpressing human T-ALL

113 In TAL1-expressing erythroid cells, the locus adopts a loop

114 We identified looping patterns unique to TAL1-expressing T-ALL cells, and, intriguingly, loops oc

115 looping facilitates both normal and aberrant TAL1 expression and may predispose to structural rearran

116 nd molecular consequences of inactivation of Tal1 expression ex vivo.

117 To better understand the events that lead to TAL1 expression in hematopoiesis and in T-ALL, we studie

118 When TAL1 expression is reduced in CEM T leukemia cells, basa

119 ATA-4 binds to the TAL1 promoter to regulate TAL1 expression positively.

120 Preleukemic studies reveal that Tal1 expression stimulates entry into the cell cycle and

121 Sirt1 knockdown reduced GATA-4 and TAL1 expression, impaired EPO effect on delayed myogenic

122 ruvate carboxykinase (encoded by ICL1, MAS1, TAL1, FBP1, and PCK1 respectively), suggestive of increa

123 ic transcription factors, such as RUNX1, SCL/TAL1, FLI1 and C/EBP family members.

124 ence of RUNX1, haematopoietic genes bind SCL/TAL1, FLI1 and C/EBPbeta and that this early priming is

125 ed transcription factor heptad (GATA2, LYL1, TAL1, FLI1, ERG, RUNX1, LMO2) binding to MEG-associated

126 Comparison of Lmo2-/- with Tal1-/- Flk-1+ cells further showed that TAL1 was requir

127 We show that TAL1 forms a positive interconnected autoregulatory loop

128 ARID5B and TAL1 frequently co-occupy target genes and coordinately

129 esis correlated with increased levels of SCL/TAL1, GATA1, GATA2, CD34, CD31, and the homeobox gene-re

130 tory shear stress, the transcription factors Tal1, Gata2, and Ets1/2 physically interacted with and r

131 The Scl (Tal1) gene encodes a helix-loop-helix transcription fact

132 We therefore propose a model in which Tal1 has distinct roles in regulating the formation of e

133 and HEB, suggesting that TAL1/E2A as well as TAL1/HEB heterodimers play a role in transformation of T

134 ATA-1 target genes, that the presence of SCL/TAL1 helps distinguish transcriptional activation versus

135 cases generally lacked overexpression of the TAL1, HOX11, HOX11L2, or the HOXA cluster genes, which h

136 To investigate the function of Tal1 in B cells, we generated Emu-TAL1 transgenic mouse

137 has implicated the bHLH transcription factor Tal1 in endocardial tube formation: in zebrafish embryos

138 a-globin genes, we reduced the expression of TAL1 in erythroid K562 cells using lentiviral short hair

139 h insights into the context-specific role of TAL1 in erythropoiesis.

140 d Emu-TAL1 transgenic mouse line, expressing Tal1 in mouse B-cell lineage.

141 To explore the role of TAL1 in transcription activation of the human gamma-glob

142 Consistent with the dual roles of TAL1 in transcription, TAL1-associated LSD1 is decreased

143 r binding of LMO2 to its partner protein SCL/TAL1 in vitro and for the function of this complex in vi

144 In addition, overexpression of TAL1 increased the gamma-globin transcription and increa

145 TAL1 increases association of the GATA-1.TAL1.LMO2.LDB1

146 PEST domain of Notch1 in our mouse model of TAL1-induced leukemia and found that 74% of the tumors h

147 ptional program by positively regulating the TAL1-induced regulatory circuit and MYC in T-ALL, thereb

148 r and represses myogenin expression, whereas TAL1 inhibits myogenin expression by decreasing MyoD bin

149 activity in vivo, we treated near-end-stage Tal1/Ink4a/Arf+/- leukemic mice with vehicle or with a G

150 nk4a)-/-, and p19(arf)-/- mice and generated tal1/ink4a/arf+/-, tal1/p16(ink4a)+/-, and tal1/p19(arf)

151 apoptosis is reduced to wild-type levels in tal1/ink4a/arf-/- mice, S phase induction remains unaffe

152 e A (PKA)-mediated phosphorylation regulates TAL1 interaction with the lysine-specific demethylase (L

153 Tal1 interacts and inhibits other helix-loop-helix facto

154 The human oncogene SCL/TAL1 interrupting locus (Stil) is highly conserved in ve

155 Here, we demonstrate that the SCL/TAL1 interrupting locus (STIL) protein interacts via its

156 that nbb is a homolog of the vertebrate SCL/TAL1 interrupting locus (Stil).

157 TAL1 is a critical transcription factor required for hem

158 TAL1 is a key hematopoietic transcription factor that bi

159 TAL1 is amongst the most frequently deregulated oncogene

160 TAL1 is an important regulator of hematopoiesis and its

161 Here, we show that TAL1 is associated with histone demethylase complexes co

162 We show that transcription factor Scl/Tal1 is essential for both establishing the hematopoieti

163 ence of LMO2, the target site recognition of TAL1 is impaired.

164 trate that aberrant miR-223 up-regulation by TAL1 is important for optimal growth of TAL1-positive T-

165 Here we show that TAL1 is normally silenced in the T-cell lineage, and tha

166 demonstrate that the DNA-binding activity of Tal1 is not required to cooperate with Lmo2 to cause leu

167 (LCR) and active globin genes, and although TAL1 is one of the two DNA-binding complex members, its

168 Using RNA interference, we demonstrated that TAL1 is required for the maintenance of the leukemic phe

169 ession of the oncogenic transcription factor TAL1 is uniquely sensitive to variations in the dosage a

170 ription factor (TF) stem cell leukaemia (Scl/Tal1) is crucial for development of these adult haemangi

171 gulator T-cell acute lymphocytic leukemia-1 (TAL1) is involved in regulating H3K27me3 variations in c

172 nal complex that contains RUNX1, GATA-3, and TAL1 itself.

173 In the TAL1 knockdown cells, the gamma-globin transcription was

174 miR-223 partially rescues T-ALL cells after TAL1 knockdown.

175 s performed using retrospective assays, that Tal1 knockout does not immediately bias precursor cells

176 While Tal1 knockout had minimal effects on cell survival and s

177 ap with the interactomes of GATA1, GATA2, or TAL1, leading to a model in which EKLF directs programs

178 XW7 protein expression, whereas knockdown of TAL1 leads to up-regulation of FBXW7 protein levels, wit

179 Yet, over half of the TAL1(+) cases lack TAL1 lesions, suggesting unrecognized (epi)genetic dereg

180 how that it acts as a major regulator of the TAL1 leukemic gene expression program.

181 miR-223 expression mirrors TAL1 levels during thymic development, with high express

182 and TAL1 or LMO1 was found in primary human TAL1/LMO1 double-positive T-ALL samples previously descr

183 tial haematopoietic regulators including Scl/Tal1, Lmo2 and PU.1.

184 sion by an enhancer complex including GATA1, TAL1, LMO2, LDB1 and Pol II at least, in erythroid cells

185 the use of tiling arrays we detected the SCL/TAL1, LMO2, Ldb1, E2A complex at all positively acting G

186 TAL1 increases association of the GATA-1.TAL1.LMO2.LDB1 transcription activation complex to the r

187 Tal1/Lmo2 and MutTAL1/Lmo2 bitransgenic mice exhibit per

188 The Ldb1/GATA-1/TAL1/LMO2 complex mediates long-range interaction betwee

189 cells indicate that LDB1, as part of a GATA1/TAL1/LMO2 complex, brings erythroid-expressed genes into

190 To address the mechanism(s) of Tal1/Lmo2 synergy in leukemia, we generated Lmo2 transge

191 into direct gene contact by the LDB1/GATA-1/TAL1/LMO2-containing complex.

192 at the haemangioblast stage to position the TAL1/LMO2/LDB1 complex to regulatory elements that are i

193 function(s) in leukemogenesis, we generated Tal1/Lmo2/Rosa26-CreER(T2)Runx1(f/f) mice and examined l

194 mately 10,000 GATA1 and approximately 15,000 TAL1 locations, which were essentially confirmed by ChIP

195 ersensitive sites across 250 kb of the human TAL1 locus in CD34+ primary stem/progenitor cells and K5

196 -ALL, we studied looping interactions at the TAL1 locus.

197 e mouse T-cell acute lymphocytic leukemia-1 (Tal1) locus, and, in addition, identified two novel elem

198 ne 172 in TAL1 specifically destabilizes the TAL1-LSD1 interaction leading to promoter H3K4 hypermeth

199 TAL1, LYL1, HOX11 and other transcription factors essent

200 Our results indicate that TAL1 may act as a bifunctional transcriptional regulator

201 el interplay between PKA phosphorylation and TAL1-mediated epigenetic regulation that regulates hemat

202 ine demethylase LSD1 may negatively regulate TAL1-mediated transcription and suggest that the dynamic

203 We conclude that TAL1-mediated up-regulation of miR-223 promotes the mali

204 y, FACS analysis of bone marrow cells in Emu-TAL1 mice revealed complete absence of B220+IgM+ and B22

205 Thus, TAL1 modulates NFKB1 expression and an NF-kappaB-depende

206 acting with conserved Ets and composite GATA/Tal1 motifs.

207 ukemia maintenance in TAL1-positive (but not TAL1-negative) T-ALL.

208 mutant, rescued the proliferative defect in Tal1-null MM precursors.

209 ccupied segments, and a subset shows reduced TAL1 occupancy and increased H3K27me3 at the transcripti

210 TAL1, together with genome-wide analysis of TAL1 occupancy by chromatin immunoprecipitation coupled

211 Furthermore, shifts in TAL1 occupancy during erythroid differentiation are asso

212 ristic molecular hallmarks, specifically Scl/TAL1 occupancy, a specific epigenetic signature, specifi

213 Genes near the GATA-2-Scl/TAL1-occupied composite elements were regulated by GATA-

214 TAL1 oncogene encodes a helix-loop-helix transcription f

215 ich creates a super-enhancer upstream of the TAL1 oncogene.

216 mated them with mice that express wild-type Tal1 or a DNA-binding mutant of TAL1.

217 LDB1, E2A, HEB, Lyl1, ETO2, and SP1, but not TAL1 or GATA proteins.

218 icant negative correlation between NFKB1 and TAL1 or LMO1 was found in primary human TAL1/LMO1 double

219 ate with the TALLMO subtype characterized by TAL1 or LMO2 rearrangements.

220 Knockdown of TAL1 or LSD1 led to a derepression of the TAL1 target ge

221 topoietic basic helix-loop-helix factors Scl/Tal1 or Lyl1.

222 y key erythroid transcription factors GATA1, TAL1, or KLF1.

223 Our results suggest that Tal1 overexpression in B cells results in a phenotype si

224 rf)-/- mice and generated tal1/ink4a/arf+/-, tal1/p16(ink4a)+/-, and tal1/p19(arf)+/- mice.

225 d tal1/ink4a/arf+/-, tal1/p16(ink4a)+/-, and tal1/p19(arf)+/- mice.

226 Sequencing reveals that >20% of monoallelic TAL1(+) patients without previously known alterations di

227 ugh blastomere transplantation, we find that tal1 plays a cell-autonomous role in regulating endocard

228 These results indicate that TAL1 plays a critical role in chromatin loop formation b

229 factor essential for leukemia maintenance in TAL1-positive (but not TAL1-negative) T-ALL.

230 demethylase inhibitor that efficiently kills TAL1-positive primary human leukemia.

231 cursor, HOXA-positive, LEF1-inactivated, and TAL1-positive subtypes, which have differentiation arres

232 n by TAL1 is important for optimal growth of TAL1-positive T-ALL cells and that sustained expression

233 During organogenesis of the kidney, SCL/Tal1(+) progenitors gave rise to endothelium and blood p

234 Overall, these results show that SCL/Tal1(+) progenitors with hemogenic capacity originate an

235 te GATA-4 expression and GATA-4 binds to the TAL1 promoter to regulate TAL1 expression positively.

236 O-R transcription start site suggesting that TAL1 promotes accessibility of this region.

237 Akt specifically phosphorylates Thr90 of the Tal1 protein within its transactivation domain in vitro

238 -Seq indicates that most DNA-bound Gata1 and Tal1 proteins are contained within higher order complexe

239 trolled by HLH inhibitors such as Id and SCL/TAL1 proteins, which recently have been suggested to pla

240 Primary and secondary xenotransplantation of TAL1-rearranged leukemia allowed development of leukemic

241 -corepressor complex during differentiation, TAL1 recruits LSD1 to the silenced p4.2 promoter in undi

242 progenitor cells, while the USF proteins and Tal1 regulate genes that specify the differentiated phen

243 tory loop that reinforces and stabilizes the TAL1-regulated oncogenic program.

244 We found that TAL1 regulates EPO-R expression mediated via three conse

245 f additional proteins lead to the model that TAL1 regulates expression after being directed to a dist

246 echanisms may facilitate the conservation of TAL1 regulation despite cis-regulatory remodeling during

247 TAL3 IgE responders, themselves a subset of TAL1 responders.

248 initial wave of mesoderm, Mesp1 binds to the Tal1 (Scl) +40 kb enhancer and generates Flk-1+ precurso

249 ignaling also accelerated the degradation of Tal1/SCL (T cell acute leukemia 1/stem cell leukemia) pr

250 ligase activity of CHIP was dispensable for Tal1/SCL binding but essential for degradation.

251 A 0.4-kb genomic DNA clone containing two Tal1/SCL binding E-boxes and GATA- and SATB1-binding mot

252 Although the TPR domain was not involved in Tal1/SCL binding, it was required for enhancing its degr

253 We found that Tal1/SCL could complex with the histone H3 lysine 9 (H3K

254 gous to the situation for E47, Notch-induced Tal1/SCL degradation not only required Skp2, a substrate

255 Notch-induced Tal1/SCL degradation was mediated by ubiquitination and

256 The oncogenic transcription factor TAL1/SCL induces an aberrant transcriptional program in

257 TAL1/SCL is a basic helix-loop-helix (bHLH) transcriptio

258 TAL1/SCL is a hematopoietic-specific oncogene and its ac

259 The oncogenic transcription factor TAL1/SCL is aberrantly expressed in 60% of cases of huma

260 The oncogenic transcription factor TAL1/SCL is aberrantly expressed in over 40% of cases of

261 basic helix-loop-helix transcription factor TAL1/SCL plays a critical role in other hematopoietic li

262 lexes and potential means by which Notch and Tal1/SCL regulate eukaryotic development.

263 les include comparative DHS mapping of known TAL1/SCL regulatory elements between human embryonic ste

264 basic helix-loop-helix transcription factor, TAL1/SCL, is required for normal erythropoiesis.

265 largely caused by aberrant activation of the TAL1/SCL, LMO1/2, and NOTCH1 oncogenes.

266 tion factors--GATA1, GATA2, RUNX1, FLI1, and TAL1/SCL--in primary human megakaryocytes.

267 elements with the blood stem cell regulator TAL1/SCL.

268 hematopoiesis-specific transcription factor Tal1/SCL.

269 dentify 71 direct transcriptional targets of TAL1/SCL.

270 regulator of hematopoiesis, SCL (also called TAL1), Snai1 and Snai2.

271 Phosphorylation of serine 172 in TAL1 specifically destabilizes the TAL1-LSD1 interaction

272 SCL/TAL1 (stem cell leukemia/T-cell acute lymphoblastic leuk

273 etween the TAL1 and STIL genes at the common TAL1/STIL breakpoints found in T-ALL.

274 Thus, Tal1 stimulates cell cycle entry independent of the ink4

275 me3-repressive mark is focally diminished in TAL1(+) T-ALLs.

276 in MEL cells resulted in derepression of the TAL1 target gene accompanied by increasing dimeH3K4 at t

277 of TAL1 or LSD1 led to a derepression of the TAL1 target genes in T-cell acute lymphoblast leukemia (

278 ile recruitment of hSET1 is increased at the TAL1 targets during erythroid differentiation.

279 wed specific expression signatures involving TAL1 targets in TAL1-expressing compared with -nonexpres

280 Flk-1+ precursors expressing Etv2 (ER71) and Tal1 that undergo hematopoietic differentiation.

281 eveal that it functions upstream of etv2 and tal1, the earliest expressed endothelial and haematopoie

282 y by an enhancer of Gata2 transcription, Scl/TAL1, thereby repressing Gata2 transcription.

283 findings reveal a novel role for GATA-4 and TAL1 to affect skeletal myogenic differentiation and EPO

284 ither p16(ink4a) or p19(arf) cooperates with Tal1 to induce leukemia in mice.

285 ice and suggest that Lmo2 may cooperate with Tal1 to interfere with E47/HEB function(s).

286 through de novo recruitment of the activator TAL1 to promote chromatin looping of distal enhancers to

287 sively parallel DNA sequencing) to GATA1 and TAL1 to study their positional organization across the m

288 the tegumental-allergen-like protein family (TAL1 to TAL13).

289 RNA) expression profiling after depletion of TAL1, together with genome-wide analysis of TAL1 occupan

290 locus to T-cell leukemogenesis, we mated our tal1 transgenic mice to ink4a/arf-/-, p16(ink4a)-/-, and

291 ied by an increase in thymocyte apoptosis in tal1 transgenic mice.

292 unction of Tal1 in B cells, we generated Emu-TAL1 transgenic mouse line, expressing Tal1 in mouse B-c

293 Translocations involving LMO2, TAL1, Ttg-1, and Hox11, as well as a recurrent interstit

294 ove background levels in cell culture (LMO2, TAL1, Ttg-1, and SIL) are also cleaved by the RAG protei

295 ith Tal1-/- Flk-1+ cells further showed that TAL1 was required to initiate or sustain Lmo2 expression

296 Promoters occupied by TAL1 were also frequently bound by the class I bHLH prot

297 completely abrogated binding of the cofactor TAL1, which binds to a separate motif.

298 s localized to a region in the C terminus of Tal1, which is evolutionarily conserved, thus suggesting

299 des a helix-loop-helix transcription factor, Tal1, which is required for blood cell development, and

300 adigm, one would predict that GATA-2 and Scl/TAL1 would commonly co-occupy such composite elements in