PMID- 11069894
OWN - NLM
STAT- MEDLINE
DCOM- 20001212
LR  - 20190605
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 14
IP  - 21
DP  - 2000 Nov 1
TI  - Context-dependent EKLF responsiveness defines the developmental specificity of 
      the human epsilon-globin gene in erythroid cells of YAC transgenic mice.
PG  - 2778-94
AB  - We explored the mechanism of definitive-stage epsilon-globin transcriptional 
      inactivity within a human beta-globin YAC expressed in transgenic mice. We 
      focused on the globin CAC and CAAT promoter motifs, as previous laboratory and 
      clinical studies indicated a pivotal role for these elements in globin gene 
      activation. A high-affinity CAC-binding site for the erythroid kruppel-like 
      factor (EKLF) was placed in the epsilon-globin promoter at a position 
      corresponding to that in the adult beta-globin promoter, thereby simultaneously 
      ablating a direct repeat (DR) element. This mutation led to EKLF-independent 
      epsilon-globin transcription during definitive erythropoiesis. A second 4-bp 
      substitution in the epsilon-globin CAAT sequence, which simultaneously disrupts a 
      second DR element, further enhanced ectopic definitive erythroid activation of 
      epsilon-globin transcription, which surprisingly became EKLF dependent. We 
      finally examined factors in nuclear extracts prepared from embryonic or adult 
      erythroid cells that bound these elements in vitro, and we identified a novel 
      DR-binding protein (DRED) whose properties are consistent with those expected for 
      a definitive-stage epsilon-globin repressor. We conclude that the suppression of 
      epsilon-globin transcription during definitive erythropoiesis is mediated by the 
      binding of a repressor that prevents EKLF from activating the epsilon-globin 
      gene.
FAU - Tanimoto, K
AU  - Tanimoto K
AD  - Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern 
      University, Evanston, Illinois 60208-3500, USA.
FAU - Liu, Q
AU  - Liu Q
FAU - Grosveld, F
AU  - Grosveld F
FAU - Bungert, J
AU  - Bungert J
FAU - Engel, J D
AU  - Engel JD
LA  - eng
GR  - CA60553/CA/NCI NIH HHS/United States
GR  - R01 DK052356-04/DK/NIDDK NIH HHS/United States
GR  - P30 CA060553/CA/NCI NIH HHS/United States
GR  - R01 DK052356/DK/NIDDK NIH HHS/United States
GR  - HL24415/HL/NHLBI NIH HHS/United States
GR  - R01 HL024415/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (COUP Transcription Factors)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Receptors, Steroid)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (erythroid Kruppel-like factor)
RN  - 9004-22-2 (Globins)
SB  - IM
MH  - Age Factors
MH  - Animals
MH  - Binding Sites
MH  - COUP Transcription Factors
MH  - Chromosome Inversion
MH  - DNA-Binding Proteins/metabolism/*physiology
MH  - Erythroid Precursor Cells/*metabolism
MH  - *Gene Expression Regulation, Developmental
MH  - Globins/*genetics
MH  - Humans
MH  - K562 Cells/metabolism
MH  - Kruppel-Like Transcription Factors
MH  - Leukemia, Erythroblastic, Acute/pathology
MH  - Mice
MH  - Mice, Transgenic
MH  - Mutagenesis, Site-Directed
MH  - Mutation
MH  - Promoter Regions, Genetic
MH  - *Receptors, Steroid
MH  - Repressor Proteins/isolation & purification/metabolism
MH  - Transcription Factors/metabolism/*physiology
MH  - Transcriptional Activation
MH  - Tumor Cells, Cultured
PMC - PMC317038
EDAT- 2000/11/09 11:00
MHDA- 2001/02/28 10:01
PMCR- 2001/05/01
CRDT- 2000/11/09 11:00
PHST- 2000/11/09 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/11/09 11:00 [entrez]
PHST- 2001/05/01 00:00 [pmc-release]
AID - 10.1101/gad.822500 [doi]
PST - ppublish
SO  - Genes Dev. 2000 Nov 1;14(21):2778-94. doi: 10.1101/gad.822500.