ライフサイエンスコーパス: gamma-globin

1 tors results in elevated expression of fetal gamma-globin.

2 ubtherapeutic levels of red cells expressing gamma-globin.

3 of BCL11A expression, and induction of fetal gamma-globin.

4 A-1, FOG-1, and Mi2 were recruited to the (A)gamma-globin -566 or (G)gamma-globin -567 GATA site when

5 recruited to the (A)gamma-globin -566 or (G)gamma-globin -567 GATA site when gamma-globin expression

6 also developed highly active TALENs to human gamma-globin, a pharmacologic target in sickle cell dise

7 our study was to identify HDACs involved in gamma-globin activation.

8 SAR-mediated induction of gamma-globin also inhibited K562 cell growth by causing

9 Gamma-globin, an oncofetal protein overexpressed by clon

10 n-globin, and the intergenic regions between gamma-globin and delta-globin genes.

11 naling pathway from HRI to ATF4 to BCL11A to gamma-globin and illustrate potential limits of murine m

12 After birth, expression of human gamma-globin and mouse embryonic globins decreased in Bc

13 Although BCL11A was shown to suppress gamma-globin and p21 and to induce MDM2 expression in th

14 ociated with significant activation of fetal gamma-globin and repression of adult beta-globin transcr

15 Expression of both gamma-globin and the lariat-embedded small interfering R

16 lt erythroblasts increased the expression of gamma-globin, and the HbF content of the cells rose to l

17 ess predominantly human beta-globin but also gamma-globin; and transgenic murine GM979 cells co-expre

18 suppression of alpha-globin and induction of gamma-globin are effective in reducing the globin chain

19 d, as is BCL11A occupancy, and both BGL3 and gamma-globin are transcribed.

20 ht into the molecular pathways that regulate gamma-globin augmentation during stress erythropoiesis.

21 creased at the (A)gamma-globin promoter when gamma-globin becomes repressed in postconception day E18

22 ly reduces BCL11A levels and increases human gamma-globin/beta-globin expression ratios.

23 Human K562 cells co-express epsilon- and gamma-globin but not beta-globin; transgenic mouse eryth

24 hy donors were able to specifically cytolyze gamma-globin(+), but not gamma-globin(-) JMML cells in a

25 Elevated levels of fetal gamma-globin can cure disorders caused by mutations in t

26 ical treatments designed to reactivate fetal gamma-globin can lead to an effective and successful cli

27 ion is evident around the time of birth, and gamma-globin chain production diminishes in postnatal li

28 ed at the transcriptional level by increased gamma-globin combined with decreased beta-globin transcr

29 ss of alpha-globin production and inadequate gamma-globin compensation lead to the development of sev

30 ntration and decreases with increasing fetal gamma-globin concentration.

31 hose of fetal cells, including increased LCR-gamma-globin contacts.

32 romoters as well as de novo formation of LCR/gamma-globin contacts.

33 herapy of JMML could be directed against the gamma-globin-derived epitope g105.

34 We predicted 5 gamma-globin-derived peptides as potential human leukocy

35 mouse embryonic globin chains to human fetal gamma globin during fetal life.

36 ns favoring development of fetal liver-like, gamma-globin expressing, definitive hematopoiesis, we fo

37 To enrich gamma-globin-expressing cells, transplanted mice were tr

38 ed reconstitution with therapeutic levels of gamma-globin-expressing cells.

39 ed in significant increases in the number of gamma-globin-expressing red cells and the amount of feta

40 f Sp1 and KLF8 resulted in elevated level of gamma globin expression in K562 cells.

41 BCL11A, a repressor of human fetal (gamma-)globin expression, is required for immune and hem

42 11A is a transcription factor that represses gamma-globin expression and fetal hemoglobin in erythroi

43 nsfected K562 and CD34(+) cells reduced both gamma-globin expression and HbF level, indicating that a

44 BCL11A is a repressor of gamma-globin expression and HbF production in adult eryt

45 r BCL11A leads to a simultaneous increase in gamma-globin expression and reduction in beta-globin exp

46 anisms involved in HU-mediated regulation of gamma-globin expression are currently unclear.

47 6 h at 5 muM, compound 3b was able to induce gamma-globin expression by nearly three times.

48 s higher during primitive erythropoiesis and gamma-globin expression continued into fetal definitive

49 ring RNA (siRNA) significantly increases the gamma-globin expression during the erythroid maturation.

50 mia, become symptomatic postnatally as fetal gamma-globin expression from two paralogous genes, hemog

51 e expression of BCL11A, a repressor of human gamma-globin expression identified by genome-wide associ

52 BCL11A is required in vivo for silencing of gamma-globin expression in adult animals, yet dispensabl

53 ined with BCL11A deficiency further enhances gamma-globin expression in adult animals.

54 ic binding sites for BCL11A results in human gamma-globin expression in mouse definitive erythroid ce

55 ed by the clinical benefit of elevated fetal gamma-globin expression in patients with sickle cell ane

56 Further increase in gamma-globin expression in primary human adult erythroid

57 that our in vivo approach resulted in stable gamma-globin expression in the majority of circulating r

58 In addition, the level of gamma-globin expression is consistently higher in MBD2-/

59 Symptoms worsen from birth as fetal gamma-globin expression is silenced.

60 DA-CIs) butyrate and trichostatin A activate gamma-globin expression via a p38 mitogen-activating pro

61 gamma-Globin expression was induced upon exposure to 5-a

62 -566 or (G)gamma-globin -567 GATA site when gamma-globin expression was low (day 18) but not when ga

63 tion has been paid to pathways that increase gamma-globin expression, and hence the production of fet

64 A-mediated knockdown significantly increased gamma-globin expression, HbF synthesis, and the percenta

65 hat HU induces SAR1, which in turn activates gamma-globin expression, predominantly through the Gialp

66 or BCL11A, a well-characterized repressor of gamma-globin expression, was significantly down-regulate

67 or beta-type globin-transgenic mice enhances gamma-globin expression.

68 determine its ability to increase levels of gamma-globin expression.

69 cing condition enhances the effect of SCF on gamma-globin expression.

70 BCL11A as a candidate negative regulator of gamma-globin expression.

71 ve chromatin mark, plays a role in silencing gamma-globin expression.

72 nd EHMT2 histone methyltransferases, induces gamma-globin expression.

73 ified several that preferentially upregulate gamma-globin expression.

74 on of a small intergenic region required for gamma-globin (fetal hemoglobin) gene silencing.

75 rate that the human epsilon- (embryonic) and gamma-globin (fetal) genes are positively regulated by K

76 High-level induction of fetal (gamma) globin gene expression for therapy of beta-hemogl

77 To test the role of CACCC box on gamma-globin gene activation, the CACCC box was deleted

78 viously considered responsible for HPFH -198 gamma-globin gene activation, was not identified.

79 ations suggest that both lentiviral-mediated gamma-globin gene addition and genetic reactivation of e

80 amined COUP-TFII as a potential repressor of gamma-globin gene after stem cell factor (SCF) stimulati

81 mediated the activation of the silent human gamma-globin gene and in CD34(+) cells, increased gamma-

82 creased interaction frequency between the (G)gamma-globin gene and LCR.

83 ical goal requires a robust understanding of gamma-globin gene and protein silencing during human dev

84 ociated with SCFAD-induced activation of the gamma-globin gene and provide a specific molecular targe

85 for BCL11A-mediated repression of endogenous gamma-globin gene and the regulatory non-coding transcri

86 betaYAC/MBD2-/- mice continue to express the gamma-globin gene at a level commensurate with 5-azacyti

87 nds to the -566 GATA site relative to the (A)gamma-globin gene cap site.

88 To investigate the control of the gamma-globin gene during development, we produced transg

89 Thus, understanding the regulation of gamma-globin gene expression and its silencing in adults

90 er hypomethylation correlates with transient gamma-globin gene expression and may explain the previou

91 trates its role in developmentally regulated gamma-globin gene expression and the ability to control

92 e investigated the effects of thalidomide on gamma-globin gene expression and the involved signaling

93 gh most studies have focused on induction of gamma-globin gene expression as an approach to induce Hb

94 , gene-selective alterations in epsilon- and gamma-globin gene expression by gain and loss of TR2/TR4

95 However, as reported here, this same gamma-globin gene expression cassette was only transcrib

96 e myeloma, thalidomide's specific effects on gamma-globin gene expression during erythroid differenti

97 der study has a functional role in silencing gamma-globin gene expression in adults.

98 effect and resulting in the up-regulation of gamma-globin gene expression in adults.

99 actor 4 (ATF4) as a novel regulator of fetal gamma-globin gene expression in human cells by repressin

100 ns in the reactivation and/or maintenance of gamma-globin gene expression in the adult transcriptiona

101 erythroid cells paradoxically enhanced fetal gamma-globin gene expression in transgenic mice, we wish

102 ing factors or drugs capable of reactivating gamma-globin gene expression is complicated by the lack

103 ggest that during definitive erythropoiesis, gamma-globin gene expression is silenced, in part, by bi

104 cally relevant transcriptional activators of gamma-globin gene expression to additively enhance HbF.

105 Fetal gamma-globin gene expression was increased in human tran

106 i2beta is sufficient to significantly induce gamma-globin gene expression without disrupting erythroi

107 vating beta-globin and indirectly repressing gamma-globin gene expression.

108 gene cluster might play a regulatory role in gamma-globin gene expression.

109 d in simian primates with a fetal pattern of gamma-globin gene expression.

110 lase and DMTU diminished thalidomide-induced gamma-globin gene expression.

111 romoter by the SCFAD is sufficient to induce gamma-globin gene expression.

112 oteins (ZF-Ldb1), leading to reactivation of gamma-globin gene expression.

113 Overcoming the silencing of the fetal gamma-globin gene has been a long-standing goal in the t

114 through which DNA methylation represses the gamma-globin gene in adult erythroid cells, betaYAC/MBD2

115 ed tissue-specific expression of a linked (A)gamma-globin gene in erythroid cells at all developmenta

116 TFII, which is involved in the regulation of gamma-globin gene induction.

117 A marked copy of the (A)gamma-globin gene inserted between locus control region

118 The fetal gamma-globin gene is expressed in fetal erythroid cells

119 The gamma-globin gene is reactivated upon treatment with the

120 Expression of the gamma-globin gene is silenced in adult humans.

121 say that detects only strong inducers of the gamma-globin gene promoter and in cultured human erythro

122 However, certain point mutations in the gamma-globin gene promoter are capable of maintaining ex

123 strating that displacement of HDAC3 from the gamma-globin gene promoter by the SCFAD is sufficient to

124 onal recruitment of RNA polymerase II to the gamma-globin gene promoter was observed with exposure to

125 as not myelotoxic, hypomethylated DNA in the gamma-globin gene promoter, and produced large cumulativ

126 HDAC3 by siRNA induced transcription of the gamma-globin gene promoter, demonstrating that displacem

127 adaptor protein NCoR, specifically from the gamma-globin gene promoter.

128 y a protein complex that binds the HPFH -198 gamma-globin gene promoter.

129 ription factor designed to interact with the gamma-globin gene promoters, or (3) a short-hairpin RNA

130 VP64, designed to interact with the proximal gamma-globin gene promoters.

131 K9Ac, which was especially pronounced at the gamma-globin gene region.

132 that O-GlcNAcylation is a novel mechanism of gamma-globin gene regulation mediated by modulating the

133 by histone deacetylases (HDACs) that mediate gamma-globin gene regulation.

134 se data support a positive role for HDAC9 in gamma-globin gene regulation.

135 rs, or (3) a short-hairpin RNA targeting the gamma-globin gene repressor, BCL11A, were tested.

136 y, we discovered that silencing of the fetal gamma-globin gene requires the erythroid-specific eIF2al

137 of a beta(m)-globin gene upstream of the (G)gamma-globin gene resulted in expression of beta(m)-glob

138 iscuss other factors that may be involved in gamma-globin gene silencing and their potential manipula

139 ch encode transcription factors critical for gamma-globin gene silencing during beta-type globin gene

140 intains the nucleosome density necessary for gamma-globin gene silencing in adults, and that LRF conf

141 observed that knockdown of Mi2beta relieves gamma-globin gene silencing in beta-YAC transgenic murin

142 ted with HDAC9 siRNA; we observed 40 and 60% gamma-globin gene silencing in day 11 (early) and day 28

143 One mode of gamma-globin gene silencing involves a GATA-1.FOG-1.Mi2b

144 HDAC9 gene knockdown produced dose-dependent gamma-globin gene silencing over an 80-320 nm range.

145 2-NuRD and GATA-1/FOG-1/NuRD, play a role in gamma-globin gene silencing, and Mi2beta (CHD4) is a cri

146 We show that lentiviral delivery of human gamma-globin gene under beta-globin regulatory control e

147 lidomide induces increased expression of the gamma-globin gene via ROS-dependent activation of the p3

148 Although the gamma-globin gene was expressed in the HPFH 2/beta locus

149 An adult stage-specific silencer of the (A)gamma-globin gene was identified between -730 and -378 r

150 a level comparable to that of the endogenous gamma-globin gene were achieved using a SB-Tn beta-globi

151 mechanisms responsible for silencing of the gamma-globin gene were obscure until application of geno

152 Lentiviral vectors encoding (1) a human gamma-globin gene with or without an insulator, (2) a sy

153 duced to 35% and chromatin looping of the (G)gamma-globin gene with the LCR was disrupted with decrea

154 lex occupancy at a site downstream of the (A)gamma-globin gene within sequences of BGL3, an intergeni

155 ed integration machinery, a micro-LCR-driven gamma-globin gene, and an MGMT(P140K) system that allowe

156 a novel transcription factor that binds the gamma-globin gene, and is essential for silencing the ga

157 -thalassemia through activation of the fetal gamma-globin gene.

158 evelopmental stage-specific transcription of gamma-globin gene.

159 and MBD2 in the silencing of the human fetal gamma-globin gene.

160 A (shRNA) within the intron of a recombinant gamma-globin gene.

161 in the beta-globin locus control region and gamma-globin gene.

162 ed by a sense-oriented intron from the human gamma-globin gene.

163 ponding to the 5'-untranslated region of the gamma-globin gene.

164 bin gene, and is essential for silencing the gamma-globin gene.

165 Re-expression of the paralogous gamma-globin genes (HBG1/2) could be a universal strateg

166 ptional activity of the endogenous beta- and gamma-globin genes and identified several that preferent

167 role in chromatin loop formation between the gamma-globin genes and LCR, which is a critical step for

168 diminished at the Ey-, betah1-, epsilon- and gamma-globin genes and locus control region in KLF1(-/-)

169 F/ZBTB7A transcription factor occupies fetal gamma-globin genes and maintains the nucleosome density

170 emonstrate that transcriptional silencing of gamma-globin genes by BCL11A involves long-range interac

171 ene-autonomous silencing of the epsilon- and gamma-globin genes during development, and suggest that

172 igenetic conditions preventing activation of gamma-globin genes during differentiation of adult eryth

173 cing of the mouse embryonic globin and human gamma-globin genes fails to occur in mice in the absence

174 ition and genetic reactivation of endogenous gamma-globin genes have potential to provide therapeutic

175 eate a natural allele at the promoter of the gamma-globin genes HBG1 and HBG2 with up to 60% efficien

176 e embryonic beta-like globin genes and human gamma-globin genes in adult erythroid cells in vivo.

177 the human embryonic epsilon-globin and fetal gamma-globin genes in definitive erythroid cells.

178 ptional or posttranscriptional events at the gamma-globin genes might underlie heterocellularity.

179 In RNA-sequencing analysis of erythroblasts, gamma-globin genes were among the most significantly upr

180 The downstream wild-type gamma-globin genes were not expressed.

181 y to the promoters of the human epsilon- and gamma-globin genes, the mouse embryonic Ey- and betah1-g

182 AL1 in transcription activation of the human gamma-globin genes, we reduced the expression of TAL1 in

183 ylation and decreased DNA methylation of the gamma-globin genes, with opposite changes in the beta-gl

184 pecific repression of the human epsilon- and gamma-globin genes.

185 ult beta-globin gene, as well as HbF and the gamma-globin genes.

186 a critical step for the transcription of the gamma-globin genes.

187 with beta-thalassaemia through induction of gamma-globin, has the potential to simultaneously suppre

188 Here we show that the human gamma-globin (HBG) genes in these mice behave as murine

189 s, HBS1L-MYB SNPs, and an SNP upstream of (G)gamma-globin (HBG2; the XmnI polymorphism), in two indep

190 ilon-globin, but in contrast to induction of gamma-globin in definitive erythroid cells.

191 a lead compound for the development of a new gamma-globin inducer.

192 activate gamma-globin synthesis or screening gamma-globin inducers for the treatment of sickle cell d

193 promoter was observed with exposure to these gamma-globin inducers.

194 ll disease and beta-thalassemia, but current gamma-globin-inducing drugs offer limited beneficial eff

195 A novel gamma-globin-inducing short-chain fatty acid derivative

196 s of HU on K562 and CD34(+) cells, including gamma-globin induction and cell-cycle regulation.

197 However, the mechanisms underlying gamma-globin induction during the rapid expansion of adu

198 1 is thus a promising therapeutic target for gamma-globin induction, and tranylcypromine may serve as

199 oint mutation associated with elevated fetal gamma-globin into erythroid cell lines.

200 improved the splicing events that remove the gamma-globin intron by optimizing the intron insertion s

201 the packaging of the spliced RNA without the gamma-globin intron by targeting the intron-containing R

202 However, the gamma-globin intron is not efficiently removed by splici

203 In contrast, human fetal gamma-globin is activated by dnTR4 only in definitive, b

204 lleviated when postnatal expression of fetal gamma-globin is maintained.

205 distinct fetal hemoglobin (HbF) stage, where gamma-globin is the dominant globin chain produced durin

206 ecifically cytolyze gamma-globin(+), but not gamma-globin(-) JMML cells in an A2-restricted manner.

207 nd Pol II in the locus and facilitates fetal gamma-globin/LCR looping and gamma-globin transcription.

208 uRD interaction and function in antagonizing gamma-globin/LCR looping.

209 pomalidomide demonstrated increased in vivo gamma-globin levels in their erythrocytes.

210 ex, was observed in erythroid cells with low gamma-globin levels, whereas only a weak signal was dete

211 fetal hemoglobin (HbF) comprising alpha- and gamma-globins may ameliorate these manifestations by mit

212 with beta-thalassemic HSCs transduced with a gamma-globin/MGMT vector initially had subtherapeutic le

213 oduced a dose-dependent 2.5-fold increase in gamma-globin mRNA (p < 0.05).

214 due to the expansion of cells lacking HbF or gamma-globin mRNA (silenced cells).

215 ions that produced low versus high levels of gamma-globin mRNA and fetal hemoglobin (HbF).

216 5-Aza that produce near maximal induction of gamma-globin mRNA and HbF do not alter cell growth, diff

217 umulation of cells that possess undetectable gamma-globin mRNA and HbF.

218 without selection, with increased levels of gamma-globin mRNA by 3.3 +/- 0.13, of gamma-globin prote

219 table SAR expression in K562 cells increased gamma-globin mRNA expression and resulted in macrocytosi

220 We found that thalidomide induced gamma-globin mRNA expression in a dose-dependent manner,

221 oreover, enforced HDAC9 expression increased gamma-globin mRNA levels by 2.5-fold with a simultaneous

222 siRNA and shRNA, we observed no induction of gamma-globin mRNA or HbF.

223 These findings highlight gamma-globin mRNA translation as a novel mechanism for r

224 -globin gene and in CD34(+) cells, increased gamma-globin mRNA, albeit only transiently.

225 uorescent, with 2.11 +/- 0.13 fold increased gamma-globin mRNA, compared to non-transfected cells.

226 duces only a small, nonadditive induction of gamma-globin mRNA, signifying that DNA methylation acts

227 adult reticulocytes, less than 5% expressed gamma-globin mRNA.

228 number of actively translating ribosomes on gamma-globin mRNA.

229 sion without affecting the expression of the gamma-globin or normal beta-globin (beta(A)) genes.

230 hemoglobin switch prior to birth, with human gamma-globin predominantly restricted to primitive eryth

231 articipate in both erythroid cell growth and gamma-globin production by regulating PI3 kinase/extrace

232 n interactions occurred in the CRE in the (G)gamma-globin promoter (G-CRE) in vitro after drug treatm

233 and dissociation of repressor complexes for gamma-globin promoter activation.

234 examining methylation patterns within the (G)gamma-globin promoter and miRNA expression within primar

235 and O-GlcNAcase (OGA), interact with the (A)gamma-globin promoter at the -566 GATA repressor site; h

236 redirected from the adult beta- to the fetal gamma-globin promoter by tethering Ldb1 to the human gam

237 We found that the proximal gamma-globin promoter complex is assembled by a developm

238 present in both the active and the repressed gamma-globin promoter complexes in fetal and adult eryth

239 ies of the active and the repressed proximal gamma-globin promoter complexes in K562 human erythroleu

240 Strikingly, targeting the SA to the fetal gamma-globin promoter in primary adult human erythroblas

241 occupancy of OGT, OGA, and Mi2beta at the (A)gamma-globin promoter is increased.

242 We also studied gamma-globin promoter methylation during in vitro differ

243 MBD2 does not bind to the gamma-globin promoter region to maintain gamma-globin si

244 ysis, we found that the highly methylated (G)gamma-globin promoter was inversely correlated to baseli

245 d Mi2beta recruitment is increased at the (A)gamma-globin promoter when gamma-globin becomes represse

246 obin promoter by tethering Ldb1 to the human gamma-globin promoter with custom-designed zinc finger (

247 binds to its target site at the human fetal gamma-globin promoter, and reactivates this transcript i

248 primary adult human erythroblasts increases gamma-globin promoter-LCR contacts, stimulating transcri

249 looping of distal enhancers to the modified gamma-globin promoter.

250 tdTomato under the control of the endogenous gamma-globin promoter.

251 us and gain of LDB1 complex occupancy at the gamma-globin promoters as well as de novo formation of L

252 lymerase that bind to the human epsilon- and gamma-globin promoters, which are activated by HS2 in K5

253 at the -566/-567 GATA sites of the proximal gamma-globin promoters.

254 els of gamma-globin mRNA by 3.3 +/- 0.13, of gamma-globin protein by 6.75 +/- 3.25 and HbF protein by

255 21 of 23 lines expressed the transgene, and gamma-globin protein was present in 100% of erythrocytes

256 throid cells had an increased beta-globin to gamma-globin ratio from 0.66+/-0.08 to 1.05+/-0.12 (p=0.

257 t decreased COUP-TFII expression resulted in gamma-globin reactivation in adult erythropoiesis.

258 In these cells, proximity between the BGL3/gamma-globin region and the LCR is established.

259 4, a known HRI-regulated protein, as a novel gamma-globin regulator.

260 Expression of human gamma-globin remained high in Bcl11a(cko/cko) embryos du

261 EHMT2 are epigenetic regulators involved in gamma-globin repression and represent a novel therapeuti

262 ther, the transcription networks involved in gamma-globin repression were selectively and differentia

263 expression is activated by KLF1, leading to gamma-globin repression.

264 ase (NuRD) chromatin complex participates in gamma-globin repression.

265 mbers, together with corepressor ETO2 and by gamma-globin repressor BCL11A.

266 creased beta-globin transcripts resulting in gamma-globin rising to 90% of total beta-like mRNA.

267 ption factor BCL11A is a central mediator of gamma-globin silencing and hemoglobin switching.

268 entiation program, leading to a reversion of gamma-globin silencing in adult human erythroblasts.

269 gene expression but is dispensable for human gamma-globin silencing in vivo.

270 the delta-globin gene that is necessary for gamma-globin silencing.

271 the gamma-globin promoter region to maintain gamma-globin silencing.

272 of BCL11A induces only partial developmental gamma-globin silencing.

273 tion acts primarily through MBD2 to maintain gamma-globin suppression in adult erythroid cells.

274 Enhanced fetal gamma-globin synthesis alleviates symptoms of beta-globi

275 Newly identified modifiers of alpha- and gamma-globin synthesis and insights into the mechanisms

276 ifying transcription factors that reactivate gamma-globin synthesis or screening gamma-globin inducer

277 Using the beta-globin and gamma-globin TALENs, we generated cell lines that expres

278 marrow CD34+ cells, with a greater effect on gamma-globin than on beta-globin.

279 enign genetic condition, mutations attenuate gamma-globin-to-beta-globin switching, causing high-leve

280 lopment of episomal vectors for the specific gamma-globin transcription activation in its native posi

281 dition, overexpression of TAL1 increased the gamma-globin transcription and increased interaction fre

282 was reactivated by an artificial zinc finger-gamma-globin transcription factor and the previously ide

283 along with GATA1, and cooperate in silencing gamma-globin transcription in adult human erythroid prog

284 Autonomous silencing of gamma-globin transcription is an important developmental

285 In contrast, when gamma-globin transcription is reactivated in these cells

286 clude that alternative NLI complexes mediate gamma-globin transcription or silencing through long-ran

287 In the TAL1 knockdown cells, the gamma-globin transcription was reduced to 35% and chroma

288 ates transcription of BCL11A, a repressor of gamma-globin transcription, by binding to its enhancer a

289 anges are accompanied by strong increases in gamma-globin transcription.

290 cilitates fetal gamma-globin/LCR looping and gamma-globin transcription.

291 on was not directly attributable to the beta/gamma-globin transcriptional unit, since this same unit

292 led to erythroid-specific expression of the gamma-globin transgene and concomitant reduction of endo

293 viral vectors to transfer wild-type beta- or gamma-globin transgenes into hematopoietic stem cells fo

294 e gene lentiviral vector encoding both human gamma-globin under the transcriptional control of erythr

295 essed beta(m)-globin throughout development; gamma-globin was co-expressed in the embryonic yolk sac,

296 bin expression was low (day 18) but not when gamma-globin was expressed (day 12).

297 whereas only a weak signal was detected when gamma-globin was expressed.

298 Human beta-globin was expressed, but gamma-globin was not; a similar expression pattern was o

299 liver proerythroblasts express low levels of gamma-globin, while adult marrow proerythroblasts expres

300 igh levels of embryonic (epsilon) and fetal (gamma) globins, with little or no adult globin (beta).