ライフサイエンスコーパス: Meis1

1 rexpression of its cofactor meis homeobox 1 (MEIS1) .

2 ecotropic viral integration site 1 homolog (MEIS1).

3 n, while forced HOXA9 expression upregulated Meis1.

4 ized by high expression of the homeobox gene MEIS1.

5 the HOX-TALE transcription factors Pbx1A and Meis1.

6 orming in a replating assay similar to Hoxa9/Meis1.

7 e genes with the strongest response to Hoxa9/Meis1.

8 ted c-Myb through up-regulation of Hoxa9 and Meis1.

9 basis of leukemogenesis involving Hoxa9 and Meis1.

10 nscription requires Pbx1 but is inhibited by Meis1.

11 enerated by proviral activation of Hoxa9 and Meis1.

12 nsisting of the homeodomain proteins PBX and MEIS1.

13 racts results in coprecipitation of PBX2 and MEIS1.

14 l cell nuclear extract contain both Pbx1 and Meis1.

15 ic leukemia factor (HLF) as a target gene of Meis1.

16 s of H3K79 methylation by Dot1l at Hoxa9 and Meis1.

17 viding self-renewing precursors that express Meis1/2 at high levels, and rapidly dividing neurogenic

18 d13 expression does not overlap with that of Meis1-3 in the developing limb; however, coexpression oc

19 Among these genes were Meis1, a known collaborator of HOX and NUP98-HOX fusion

20 ne Ascl1 (Mash1) and increased expression of Meis1, a marker of postmitotic LGE neurons.

21 This includes Meis1, a TALE class homeobox transcription factor requir

22 mouse models of leukemia produced by Hoxa9, Meis1 accelerates leukemogenesis.

23 together with its trimeric partners PBX1 and MEIS1, activate p21 transcription, resulting in cell cyc

24 oxA9, Pbx1 and Meis1, exaggerated HoxA9-Pbx1-Meis1 activity, and progenitor transformation in collabo

25 Expression of Meis1 alone did not immortalize any factor-dependent mar

26 Although MEIS1 alone has only a moderate effect on cell prolifera

27 Meis1 alone transforms Prep1-deficient fibroblasts, wher

28 Meis1 also cooperatively binds CRS1 with the Pbx homolog

29 demonstrate that the mouse ortholog of hth, Meis1, also encodes a HDless isoform, suggesting that ho

30 hrough aberrant activation of Hoxa genes and Meis1, among others.

31 ion of proleukemogenic target genes, such as MEIS1 and Bcl2.

32 with other leukemic oncogenes, such as Hoxa9/Meis1 and E2A-HLF, did not.

33 Coexpression of the homeodomain protein Meis1 and either HoxA7 or HoxA9 is characteristic of man

34 Targeting Hoxa9/Meis1 and Fas by miR-196b is probably also important for

35 LL to chromatin sites in target promoters of MEIS1 and HOXA genes.

36 Meis1 and Hoxa9 expression is upregulated by retroviral

37 t to cause rapid AML, while co-expression of Meis1 and Hoxa9 induces rapid AML.

38 Homeobox transcription factors Meis1 and Hoxa9 promote hematopoietic progenitor self-re

39 leading to the expression of factors such as MEIS1 and HOXA9, which in turn can replace MLL-fusion pr

40 es the expression levels of MLL target genes MEIS1 and HOXA9.

41 ated by Mll-AF9 and its downstream effectors Meis1 and Hoxa9.

42 d maintenance of MLL transformation requires Meis1 and is codependent on the redundant contributions

43 Here, we demonstrate that both Meis1 and its relative, pKnox1, dimerize with Pbx1 on th

44 In mice, Meis1 and Meis2 are developmentally expressed in a patte

45 mical and transgenic experiments reveal that Meis1 and Meis2 bind a specific sequence in the Pax6 len

46 Overexpression of Meis1 and Meis2 greatly enhanced the formation of hemato

47 Here we show that the Meis1 and Meis2 homeoproteins are direct regulators of P

48 und that endogenous Mesp1 indirectly induces Meis1 and Meis2 in endothelial cells derived from embryo

49 x genes of the A and B cluster as well as of Meis1 and Pim-1 and down-modulation of globin genes and

50 The different levels of Meis1 and the presence of Prep1 are followed at the tran

51 Inclusion of Mycn and Meis1 and use of polycistronic viruses increase reprogra

52 oderm to cardiac mesoderm), meis homeobox 1 (MEIS1) and GATA-binding protein 4 (GATA4) (postcardiac m

53 Interestingly, p21, Meis1, and a novel cell-cycle inhibitory gene, Btg2, are

54 y represses cell-cycle inhibitory genes p21, Meis1, and Btg2, promotes adult CM proliferation; and pr

55 MOZ may reduce the proliferative capacity of MEIS1, and HOX-driven lymphoma and leukemia cells.

56 In myeloid cells, HOXA9, MEIS1, and PBX2 are all strongly expressed in the nucleu

57 y mediated by effects on its partner protein MEIS1, and potentially due to two newly identified nucle

58 Thus, the leukemia-promoting properties of Meis1 are at least partly mediated by a low-oxidative st

59 We determined that HOXA9 and MEIS1 are coexpressed with MN1 in a subset of clinical M

60 The genes encoding Hoxa9 and Meis1 are transcriptionally coactivated in a subset of a

61 rmore, our studies demonstrate that PBX3 and MEIS1 are two direct target genes of miR-495, and forced

62 bdominal-type HoxA genes in combination with Meis1 are well-documented on-cogenes in various leukemia

63 Here we identify Meis1 as a critical regulator of the cardiomyocyte cell

64 These results identify Meis1 as a critical transcriptional regulator of cardiom

65 HOXA9 protein, we serendipitously identified Meis1 as a HOXA9 regulatory target.

66 ome-wide association studies have identified Meis1 as a risk factor for SCD.

67 which includes the homeobox genes Hoxa9 and Meis1 as key components.

68 id progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways.

69 eq, we show that 5 of the 68 loci pinpoint a MEIS1 binding event within a group of 252 MK-overexpress

70 cus in DNM3, regulating platelet volume, the MEIS1 binding site falls within a region acting as an al

71 Many Hoxa9 and Meis1 binding sites are also bound by PU.1 and other lin

72 Because Meis1 binds N-terminal Hoxa9 sequences that are replaced

73 uding previously described targets Hoxa9 and Meis1 but also Mecom and Eya1, and much larger groups of

74 Surprisingly, Vp16-Meis1 (but not engrailed-Meis1) functioned as an autonom

75 for normal hematopoiesis, the regulation of Meis1 by its partner protein is of interest.

76 Although Meis1 can be overexpressed in bone marrow long-term repo

77 Although Hoxa9 and Meis1 can bind DNA as heterodimers, both can also hetero

78 Hoxa9 and the Hox cofactor Meis1 cobind at hundreds of highly evolutionarily conser

79 that Nup98-HoxA9, indeed mimicks Hoxa9 plus Meis1 coexpression - it immortalizes myeloid progenitors

80 Pbx1, another Meis1 cofactor, also induces apoptosis; however, coexpre

81 The functions of the Hox/Meis1 complex in leukemia, however, remain elusive.

82 These results indicate that PBX-MEIS1 complexes interact with nuclear T3 receptors to en

83 promoters that drive leukemogenesis and that Meis1 CTD and Hox NTD cooperate in gene activation.

84 replaces the essential functions of both the Meis1 CTD and Hoxa9 NTD suggests that Meis-Pbx and Hox-P

85 p1 posttranslationally controls the level of Meis1, decreasing its stability by sequestering Pbx1.

86 ls as well as gene expression alterations in MEIS1-deficent cells and identified synaptotagmin-like 1

87 Replacement of SYTL1 in MEIS1-deficent cells restored both cell migration and en

88 ympathetic target-field innervation and that Meis1 deficient sympathetic neurons die by apoptosis fro

89 ive stress, rescuing leukemia development in Meis1-deficient cells.

90 Here we show that Meis1-deficient embryos have partially duplicated retina

91 In addition, Meis1-deficient embryos lack well-formed capillaries, al

92 BM cells of Meis1-deficient mice showed reduced colony formation and

93 Inducible Meis1 deletion in adult mouse HSCs resulted in loss of H

94 Meis1 deletion in mouse cardiomyocytes was sufficient fo

95 Further, we found that Meis1 deletion led to the accumulation of reactive oxyge

96 L) protein led to reversal of the effects of Meis1 deletion.

97 Syk upregulation occurs through a Meis1-dependent feedback loop.

98 Coexpression of MEIS1 dramatically shortened the onset of AML.

99 ockdown of FABP4 increases survival in Hoxa9/Meis1-driven AML model.

100 ating several leukemogenic features of Hoxa9/Meis1-driven leukemia.

101 loop, prolonging survival of mice with Hoxa9/Meis1-driven leukemia.

102 The transcription factor Meis1 drives myeloid leukemogenesis in the context of Ho

103 These data indicate that HOXA9 modulates Meis1 during normal murine hematopoiesis.

104 hat Gfi1 directly represses HoxA9, Pbx1, and Meis1 during normal myelopoiesis.

105 duced neuronal differentiation in the LGE of Meis1(-/-) embryos.

106 CRISPR/Cas9-mediated ablation of a putative Meis1 enhancer carrying DNMT3A(R882H)-induced DNA hypome

107 MEIS1 enhances in vitro HOXA9-PBX protein complex format

108 s exhibit elevated levels of HoxA9, Pbx1 and Meis1, exaggerated HoxA9-Pbx1-Meis1 activity, and progen

109 These results show that Meis1 exerts 2 independent functions, with its role in p

110 l progenitors, and a concomitant increase of Meis1-expressing cells, were observed in primary cell cu

111 s required for positioning the boundaries of Meis1-expressing cells.

112 amino terminal MLL sequences down-regulates Meis1 expression and inhibits cell proliferation, sugges

113 TPO also controlled MEIS1 expression at mRNA levels, at least in part due to

114 In these studies, we knocked down Meis1 expression by shRNA lentivirus transduction in mur

115 These results show that MEIS1 expression is important for MLL-rearranged leukemi

116 Hoxa9 and Meis1 expression was correlated in hematopoietic progeni

117 MLL-FRYL did not increase MEIS1 expression, conferred a proliferative advantage wi

118 These progenitors lacked Meis1 expression, could not proliferate in stem cell fac

119 alizes myeloid progenitors in the absence of Meis1 expression, the contribution of Meis1 toward leuke

120 ow transplantation through suppressing Hoxa9/Meis1 expression.

121 g that CREB1 may mediate HOXA9 modulation of Meis1 expression.

122 o cause rapid AML in the absence of enforced Meis1 expression.

123 A(R882H)-induced DNA hypomethylation impairs Meis1 expression.

124 the Meis1 locus in pre-B-cells and maintains Meis1 expression.

125 ecific transcription factors (Hox(s), Gata3, Meis1, Eya1 and Pbx1), and enforced their active gene tr

126 d MYB and thereby interfering with the HOXA9/MEIS1/FLT3/MYB signaling network, which in turn caused d

127 data suggest that in myeloid leukemia cells MEIS1 forms trimeric complexes with PBX and HOXA9, which

128 Myeloid ecotropic viral integration site 1 (Meis1) forms a heterodimer with Pbx1 that augments Hox-d

129 6-Meis1-mediated transformation required the Meis1 function of binding to Pbx and DNA but not its C-t

130 Surprisingly, Vp16-Meis1 (but not engrailed-Meis1) functioned as an autonomous oncoprotein that mimi

131 A, follistatin), homeo domain (HoxD1, Meis2, Meis1, Gbx2), IGF (IGFBP3, IGFBP6, CTGF), Notch (manic f

132 ylation, an unexpected decrease in HOXA9 and MEIS1 gene expression, and decreased MLL and menin occup

133 anscription of the cellular Hoxa9, Hoxa7 and Meis1 genes at levels similar to those found in mouse AM

134 9 methylation, and up-regulation of Hoxa and Meis1 genes underlie the molecular mechanism of how DOT1

135 MV4-11 is known to overexpress the HOXA9 and MEIS1 genes, whereas D283 overexpresses the OTX2 homeobo

136 , as well as of those of coexpressed HOX and MEIS1 genes.

137 emias has been linked to upregulation of HOX/MEIS1 genes.

138 In a HoxA9-Meis1 (H9M) model of acute myeloid leukemia (AML), we fo

139 Region E contains four consecutive PBX/MEIS1 half-sites.

140 Among these, variants in MEIS1 have emerged as the largest risk factors for RLS,

141 HOXA9 and MEIS1 have essential oncogenic roles in mixed lineage le

142 PBX-MEIS1 heterodimers bind the first and second half-sites,

143 HOX genes--HOXA9, HOXA10, and HOXC6--and the MEIS1 HOX coregulator (P <.008, one-sided Wilcoxon test)

144 Meis1(+/-) Hoxa9(-/-) deficient mice, generated to test

145 ould provide a strong selective advantage to Meis1-HoxA9 coexpressing cells in vivo, leading to leuke

146 Meis1-HoxA9 cooperation suppresses several myeloid diffe

147 And, although Nup98-HOXA9, MEIS1-HOXA9, and E2A-Hlf could transform ME-deficient ce

148 ing mitochondrial Fh1 efficiently propagated Meis1/Hoxa9-driven leukemia.

149 ce of endogenous Hox gene expression in Vp16-Meis1-immortalized progenitors allowed us to investigate

150 nced by (1) proviral activation of Hoxa9 and Meis1 in BXH-2 murine AML, (2) formation of the chimeric

151 In contrast, overexpression of Meis1 in cardiomyocytes decreased neonatal myocyte proli

152 kin mice to decipher the mechanistic role of Meis1 in established MLL leukemia.

153 However, the functions of Meis1 in hematopoiesis remain largely unknown.

154 Here we identified 2 independent actions of Meis1 in hematopoietic development: one regulating cellu

155 More importantly, the primary function of Meis1 in HSCs remains unknown.

156 , and (3) the strong expression of HoxA9 and Meis1 in human AML.

157 shRNA-mediated knockdown of MEIS1 in human MLL-fusion gene leukemia cell lines resul

158 ematopoiesis was sustained in the absence of Meis1 in inducible knock-out mice.

159 The role of Meis1 in leukemia is well established, but its role in h

160 We analyzed global DNA binding of MEIS1 in leukemic cells as well as gene expression alter

161 stream MLL-regulated genes such as HOXA9 and MEIS1 In light of developing a therapeutic strategy targ

162 Meis1 in particular serves a major role in establishing

163 LL-ENL) oncoprotein to overexpress Hoxa9 and Meis1 in primary hematopoietic cells.

164 Such data point to role of Meis1 in striatal development, also supported by reduced

165 ow show that in vitro DNA site selection for MEIS1 in the presence of HOXA9 and PBX yields a consensu

166 Ectopic expression of Meis1 in these Hoxa9 cells suppressed their G-CSF-induce

167 of Rab5(+) endosomes is severely altered in Meis1-inactivated sympathetic neurons.

168 We report that Meis1 inactivation in the mouse neural crest leads to an

169 ve (phospho)proteomic analysis revealed that Meis1 increased Syk protein expression and activity.

170 nt mice in vivo, we found that Sox2 dose and Meis1 - independent of Pbx co-factors - regulate Ascl1 e

171 hat MYB expression is regulated by Hoxa9 and Meis1, indicating the existence of an autoregulatory fee

172 primary and secondary murine models of Hoxa9/Meis1-induced leukemia.

173 uency of leukemia stem cells (LSCs) in Hoxa9+Meis1-induced leukemias.

174 etic progenitors significantly impairs Hoxa9/Meis1-induced leukemic transformation.

175 The decrease of Meis1 prevents Meis1 interaction with Ddx3x and Ddx5, which are essenti

176 These results suggest that Meis1 interacts with various trophic factors signaling p

177 Meis1 is a homeodomain transcription factor coexpressed

178 We demonstrated that Meis1 is a major regulator of sympathetic target-field i

179 We demonstrate that Meis1 is essential for maintenance of established leukem

180 These and other studies showing that Meis1 is expressed at high levels in hematopoietic stem

181 The transcription factor Meis1 is expressed preferentially in hematopoietic stem

182 The homeodomain transcription factor Meis1 is required for normal cardiac development but its

183 We hypothesize that Meis1 is required for the homing and survival of leukemi

184 In the present study, we found that Meis1 is required for the maintenance of hematopoiesis u

185 ell-committed progenitors, coexpression with Meis1 is required for the production of AML-initiating p

186 Finally, we show that Meis1 is required for transcriptional activation of the

187 etrovirally driven coexpression of HOXA9 and MEIS1 is sufficient to induce myeloid leukemia in mice.

188 The homeobox transcription factor MEIS1 is uniquely transcribed in megakaryocytes and not

189 myeloid ecotropic viral integration site-1 (Meis1) is an oncogene.

190 that seven of them (Dlx3, Dlx5, Dlx6, Msx1, Meis1, Isl1, and Pitx1) are zonally expressed.

191 or cooperative transformation with wild-type Meis1, it was dispensable in Vp16-Meis1 progenitors.

192 Meis1 knockdown resulted in decreased proliferation and

193 tion recipients was significantly delayed by Meis1 knockdown.

194 active oxygen species where treatment of the Meis1 knockout mice with the scavenger N-acetylcystein r

195 Finally, we demonstrate that the effect of Meis1 knockout on HSCs is entirely mediated through reac

196 Here, we used inducible Meis1-knockout mice coupled with MLL-AF9 knockin mice to

197 Meis1 leukemogenesis functions required binding to Pbx,

198 nt for transcription activation at HOXA9 and MEIS1 loci and that this activity is evolutionarily cons

199 We demonstrate that MOZ localizes to the Meis1 locus in pre-B-cells and maintains Meis1 expressio

200 odel and human leukemia cells, we found that Meis1 loss led to increased oxidative stress, oxygen flu

201 Our data link MEIS1 loss of function to the etiopathology of RLS, high

202 hematopoietic stem cells (HSCs) suggest that Meis1 may also be required for the proliferation/self-re

203 This previously unrecognized action of Meis1 may explain the embryonic lethality observed in Me

204 Targeting MEIS1 may have therapeutic potential for treating leukem

205 cription and H2B ubiquitination of Hoxa9 and Meis1 Mechanistically, H3 and PAF1 competed for ENL inte

206 yb is essential but not sufficient for Hoxa9/Meis1 mediated transformation.

207 s a critical collaborator required for Hoxa9/Meis1-mediated leukemogenesis.

208 taining the proliferation required for Hoxa9/Meis1-mediated leukemogenesis.

209 Vp16-Meis1-mediated transformation required the Meis1 functio

210 explain the embryonic lethality observed in Meis1(-/-) mice that arises from failure of lymphatic-ve

211 ansfection of HOXA9 and PBX2 with or without MEIS1 minimally influences transcription of a reporter g

212 genes critical for leukemogenicity including Meis1, Mn1, and Hoxa gene cluster.

213 B1 in Hoxa9(-/-) bone marrow cells increased Meis1 mRNA almost as well as HOXA9, suggesting that CREB

214 Loss of Hoxa9 caused downregulation of the Meis1 mRNA and protein, while forced HOXA9 expression up

215 eis1, were small and had reduced bone marrow Meis1 mRNA and significant defects in fluorescence-activ

216 Meis1 (Myeloid Ecotropic viral Integration Site 1) is a

217 nt with their roles in hindbrain patterning, MEIS1, NKX6-1, as well as HOX and POU family binding mot

218 binding sites for Hoxa9 and the Hox cofactor Meis1 on a genome-wide level and profiled their associat

219 Here, we examined the effect of loss of Meis1 on HSC function and metabolism.

220 the biochemical functions of both Hoxa9 and Meis1 on target gene promoters and might evoke their sam

221 pitation confirmed co-occupancy of Hoxa9 and Meis1 on the Flt3 promoter.

222 These studies also suggest overexpression of Meis1 or Nup98-hoxA9 represses myeloid-specific gene tra

223 ne--in the absence of coexpressed retroviral Meis1 or of expression of endogenous Meis genes--blocks

224 tly generated 2 phenotypically similar Hoxa9+Meis1 overexpressing acute myeloid leukemias that differ

225 nsforms murine bone marrow cells, concurrent Meis1 overexpression greatly accelerates oncogenesis.

226 We now report that Meis1 overexpression strongly induces apoptosis in a var

227 e MLL-leukemia stem cells, including HOXA10, MEIS1, PBX3, and MEF2C.

228 aled overexpression of FLT3, homeobox genes (MEIS1, PBX3, HOXB3), and immunotherapeutic tar-gets (WT1

229 our data delineate an MLL-fusion/Tet1/Hoxa9/Meis1/Pbx3 signaling axis in MLL-rearranged leukemia and

230 The Meis1/pKnox1-interaction domain in Pbx1 resided predomin

231 A wide range of data suggests that HOXA9 and MEIS1 play a synergistic causative role in AML, although

232 Since HOXA9 and MEIS1 play key developmental roles, are cooperating DNA

233 protein that mimicked combined activities of Meis1 plus Hoxa9, immortalizing early progenitors, induc

234 oxa9)/myeloid ecotropic viral integration 1 (Meis1)/pre-B-cell leukemia homeobox 3 (Pbx3) genes.

235 Here, we report that Pbx-Meis1/Prep1 binds DNA cooperatively with heterodimers of

236 ace restored heterodimerization with Hox and Meis1/Prep1 proteins.

237 equired for cooperative DNA binding with Pbx-Meis1/Prep1.

238 The decrease of Meis1 prevents Meis1 interaction with Ddx3x and Ddx5, wh

239 erentiation; the suppression of a HoxA9-Pbx1-Meis1 progenitor program and the induction of a granulop

240 ion of Meis1-related signature genes in Vp16-Meis1 progenitors.

241 wild-type Meis1, it was dispensable in Vp16-Meis1 progenitors.

242 Coexpressed Meis1 programmed rapid AML-initiating character, maintai

243 escribe a cultured progenitor model in which Meis1 programs leukemogenicity.

244 is did not reveal direct binding of HOXA9 to Meis1 promoter/enhancer regions.

245 or MLL-rearranged leukemias and suggest that MEIS1 promotes cell-cycle entry.

246 models of leukemogenesis, we have shown that MEIS1 promotes leukemic cell homing and engraftment in b

247 esults of the present study demonstrate that Meis1 protects and preserves HSCs by restricting oxidati

248 Hoxa9 overexpression, Syk signaling induces Meis1, recapitulating several leukemogenic features of H

249 While we previously showed that Meis1 regulates Hif-1alpha transcription in vitro, we de

250 In addition, we showed that Meis1 regulates the transcription of key molecules neces

251 l genes, including Cd34 and Flt3 (defined as Meis1-related leukemic signature genes).

252 leukemic aggressiveness and transcription of Meis1-related signature genes in Vp16-Meis1 progenitors.

253 rogenitors, inducing low-level expression of Meis1-related signature genes, and causing leukemia with

254 nisms leading to transformation by HOXA9 and MEIS1 remain elusive.

255 t a dominant transactivation domain fused to Meis1 replaces the essential functions of both the Meis1

256 Second, overexpression of Meis1 repressed the development of early erythroid proge

257 Meis1 requires a functional homeodomain and Pbx-interact

258 menin, ectopic expression of both Hoxa9 and Meis1 rescues colony formation defects in Men1-excised b

259 n in vitro, we demonstrate here that loss of Meis1 results in down-regulation of both Hif-1alpha and

260 hin BTBD9 (rs3923809), TOX3 (rs3104788), and MEIS1 (rs2300478) genes were significantly associated wi

261 ations with 4 other hematopoietic TFs (Fli1, Meis1, Runx1, and Scl) to regulate distinct sets of path

262 lizing previously reported associations with MEIS1, SCN5A, ARHGAP24, CAV1, and TBX5 to African Americ

263 xpression profiling of cells transduced with Meis1 shRNA showed reduced expression of genes associate

264 verticalmiR-150 dash, verticalFLT3/MYB/HOXA9/MEIS1 signaling circuit underlying the pathogenesis of l

265 ant treatment, and specific BTBD9, TOX3, and MEIS1 SNP distribution are independent predictors of PLM

266 RA-associated transcription of Nr2F1, Nr2F2, Meis1, Sox9 and BMP2, but had no effect on the Hoxa5, Ho

267 The TALE-class homeoprotein MEIS1 specifically collaborates with HOXA9 to drive myel

268 es compromised the function of the canonical MEIS1 splice isoform but were irrelevant to an isoform k

269 tumor-inhibiting activity is the control of Meis1 stability.

270 we confirmed that miR-204 targets HOXA10 and MEIS1, suggesting that the HOX up-regulation observed in

271 Coexpressing HoxA9 with Meis1 suppresses this apoptosis and provides protection

272 hat heterodimers containing Pbx/Prep1 or Pbx/Meis1 TALE homeodomain proteins bind to four functional

273 The MEIS1 target gene of typical MLL fusion oncoproteins was

274 in-like 1 (Sytl1, also known as Slp1) as the MEIS1 target gene that cooperates with Hoxa9 in leukemog

275 ample of a transcription factor oncoprotein (Meis1) that establishes expression of a tyrosine kinase

276 whose expression is indirectly regulated by Meis1 through the transcription factor PU.1.

277 Together, our results reveal that MEIS1, through induction of SYTL1, promotes leukemogenes

278 loci associated with insomnia symptoms (near MEIS1, TMEM132E, CYCL1 and TGFBI in females and WDR27 in

279 trans-repressing (engrailed fusion) forms of Meis1 to define its biochemical functions that contribut

280 he growth-promoting DNA binding landscape of Meis1 to the growth-controlling landscape of Prep1.

281 nce of Meis1 expression, the contribution of Meis1 toward leukemia remains unclear.

282 GSK3) plays a critical role in mediating Hox/MEIS1 transcriptional program and its inhibition shows p

283 a is required for the proliferation of Hoxa9/Meis1-transformed cells in culture and that loss of C/EB

284 with Ddx3x and Ddx5, which are essential for Meis1 tumorigenesis, and modifies the growth-promoting D

285 lasts, whereas Prep1 overexpression inhibits Meis1 tumorigenicity.

286 We observed a significant excess of rare MEIS1 variants in individuals with RLS.

287 MEIS1 was confirmed as the strongest genetic risk factor

288 ction of effect, and total genetic burden of MEIS1, we interrogated 188 case subjects and 182 control

289 whereas negative cell-cycle regulators (p21, Meis1) were decreased in Tbx20(OE) hearts compared with

290 Several transcription factors, including Meis1, were methylated and silenced during differentiati

291 ucts have previously been reported to induce Meis1, were shown to be direct targets of HOXA9.

292 rated to test HOXA9 regulation of endogenous Meis1, were small and had reduced bone marrow Meis1 mRNA

293 genes (e.g., HOX A5, HOXA9, and HOXA10) and MEIS1, which are the typical hallmark of MLL rearrangeme

294 Disruption of Meis1, which encodes a Pbx DNA-binding partner, results

295 re was also an increase in the expression of Meis1, which has been linked to cardiomyocyte cell cycle

296 enforce persistent expression of Hox a9 and Meis1, which is pivotal for leukemogenesis through mecha

297 expression of HOX genes and the HOX cofactor MEIS1, which is pivotal for leukemogenesis.

298 xes which appear to contain HOXA9, PBX2, and MEIS1, while immunoprecipitation of HOXA9 from these ext

299 We previously isolated a Xenopus homolog of Meis1 (Xmeis1).

300 arly granule cell progenitor markers (MATH1, MEIS1, ZIC1), mitogens (SHH, JAG1) that control prolifer