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

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

5 , a known interacting protein of both AR and MEIS1.

6 n, while forced HOXA9 expression upregulated Meis1.

7 ized by high expression of the homeobox gene MEIS1.

8 the HOX-TALE transcription factors Pbx1A and Meis1.

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

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

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

12 basis of leukemogenesis involving Hoxa9 and Meis1.

13 nscription requires Pbx1 but is inhibited by Meis1.

14 ge concurrently with decreased expression of MEIS1.

15 A9 protein with its TALE cofactors, PBX1 and MEIS1.

16 th short interfering RNA (siRNA) to suppress MEIS1.

17 HOXB13 mutants and oncogenic cofactors when MEIS1/2 are silenced.

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

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

20 y are associated with the down-regulation of MEIS1, a HOX-family transcription factor.

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

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

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

24 of preexisting cardiomyocytes(1,2) and that Meis1, a three amino acid loop extension (TALE) family h

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

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

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

28 Meis1 alone transforms Prep1-deficient fibroblasts, wher

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 leukemia cells expressed increased levels of MEIS1, an important leukemogenic MLL target gene that pl

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

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

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

35 gene, acting as a downstream target of both MEIS1 and EWS-FLI1, is also characterized as a novel tum

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

37 d several of their partner proteins, such as MEIS1 and FOXC1, which have been demonstrated to be caus

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

39 Meis1 and Hoxa9 expression is upregulated by retroviral

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

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

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

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

44 cipitation with sequencing demonstrates that Meis1 and Hoxb13 act cooperatively to regulate cardiomyo

45 These results demonstrate that Meis1 and Hoxb13 act cooperatively to regulate cardiomyo

46 ate cancer cells increased the expression of MEIS1 and increased the occupancy of MYC at the MEIS1 lo

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

48 f MEIS proteins results in downregulation of Meis1 and MEIS1 target gene expression including Hif-1al

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

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

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

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

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

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

55 2f2 (Nr2f2) in addition to Meis homeobox 1 (Meis1) and Meis homeobox 2 (Meis2) gene family members w

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

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

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

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

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

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

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

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

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

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

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

67 We also identified MEIS1 as a potential pharmacodynamic biomarker of treatm

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

69 Through integrative analysis, we identify MEIS1 as a super-enhancer-driven oncogene, which co-oper

70 Our analyses identify Pbx3 and Meis1 as critical regulators of tail regeneration and ax

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

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

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

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

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

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

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

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

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

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

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

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

83 We reasoned that MEIS1 could have a similar role in the developing heart.

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

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

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

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

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

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

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

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 ns including decorin (DCN) as a mechanism of MEIS1-driven tumor suppression.

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

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

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

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

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

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 lnerability in a subset of low HIF1alpha/low MEIS1-expressing MLL-rearranged leukemia cells.

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

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

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

116 We hypothesized that suppression of MEIS1 expression in fetal sheep cardiomyocytes leads to

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

118 er samples and the prostate TCGA cohort that MEIS1 expression is inversely proportional to AR activit

119 Here we show that MEIS1 expression is sufficient to decrease proliferation

120 MEIS1 expression was also variable in a pediatric MLL-re

121 Hoxa9 and Meis1 expression was correlated in hematopoietic progeni

122 xpression of glycolytic genes decreased when MEIS1 expression was suppressed.

123 MYC immunohistochemistry, MYC activity, and MEIS1 expression were inversely correlated.

124 s functions in a negative role in regulating MEIS1 expression, and that this down-regulation may cont

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

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

127 ow transplantation through suppressing Hoxa9/Meis1 expression.

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

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

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

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

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

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

134 6-Meis1-mediated transformation required the Meis1 function of binding to Pbx and DNA but not its C-t

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

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

137 9 methylation, and up-regulation of Hoxa and Meis1 genes underlie the molecular mechanism of how DOT1

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

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

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

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

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

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

144 Meis1-HoxA9 cooperation suppresses several myeloid diffe

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

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

147 Moreover, adult Meis1-Hoxb13 double-knockout hearts display widespread c

148 ults define and underscore the importance of MEIS1-HOXB13 transcriptional regulation in suppressing p

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

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

151 ositive loci at the Hoxa/b gene clusters and Meis1 in ChIP-seq, together with NMR analysis of the H3K

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

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

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

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

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

161 Meis1 in particular serves a major role in establishing

162 we report that Hoxb13 acts as a cofactor of Meis1 in postnatal cardiomyocytes.

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

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

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

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

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

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

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

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

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

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

175 Meis1 is a homeodomain transcription factor coexpressed

176 Thus, we conclude that MEIS1 is a key regulator of cardiomyocyte metabolism and

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

178 rates that the tumor-suppressive activity of MEIS1 is dependent on HOXB13.

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

180 The transcription factor Meis1 is expressed preferentially in hematopoietic stem

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

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

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

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

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

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

187 Myeloid ecotropic viral integration site 1 (MEIS1) is a transcription factor that promotes glycolysi

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

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

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

191 Meis1 knockdown resulted in decreased proliferation and

192 tion recipients was significantly delayed by Meis1 knockdown.

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

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

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

196 Meis1 leukemogenesis functions required binding to Pbx,

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

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

199 S1 and increased the occupancy of MYC at the MEIS1 locus.

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

203 Targeting MEIS1 may have therapeutic potential for treating leukem

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

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

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

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

208 Vp16-Meis1-mediated transformation required the Meis1 functio

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

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

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

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

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

214 -B-cell leukemia transcription factor 1) and MEIS1 (myeloid ecotropic viral integration site 1 homolo

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

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

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

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

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

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

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

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

223 n through direct effects on the HOX cofactor MEIS1, paving the way for clinical trials.

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

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

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

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

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

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

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

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

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

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

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

235 Coexpressed Meis1 programmed rapid AML-initiating character, maintai

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

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

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

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

240 Down-regulation of MEIS1 promotes the maturation of oxidative phosphorylati

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

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

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

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

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

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

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

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

249 However, small molecule inhibitors of MEIS1 remained unknown.

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

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

252 Meis1 requires a functional homeodomain and Pbx-interact

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

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

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

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

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

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

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

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

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

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

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

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

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

266 rentiation, while Hox-mediated activation of Meis1 suppresses myeloid differentiation.

267 MEIS1 suppression with siRNA increased maximal oxygen co

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

269 teins results in downregulation of Meis1 and MEIS1 target gene expression including Hif-1alpha, Hif-2

270 The MEIS1 target gene of typical MLL fusion oncoproteins was

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

272 This led us to develop inhibitors of MEIS1 that could modulate HSC activity.

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

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

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

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

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

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

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

280 gene expression, with downregulation of the MEIS1 transcription factor and its transcriptional targe

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

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

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

284 lasts, whereas Prep1 overexpression inhibits Meis1 tumorigenicity.

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

286 Expression of MEIS1 was assayed in left ventricular cardiac tissue and

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 Meis1, which belongs to TALE-type class of homeobox gene

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

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

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

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

299 olism and that the normal down-regulation of MEIS1 with age underlies a gradual switch to oxidative m

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