PMID- 9122214
OWN - NLM
STAT- MEDLINE
DCOM- 19970424
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 94
IP  - 6
DP  - 1997 Mar 18
TI  - Binary transgenic mouse model for studying the trans control of globin gene 
      switching: evidence that GATA-1 is an in vivo repressor of human epsilon gene 
      expression.
PG  - 2444-8
AB  - To test whether human GATA-1 (hGATA-1) is involved in the transcriptional control 
      of globin gene switching, we produced transgenic mice overexpressing hGATA-1, 
      crossed them with mice carrying a human beta-globin locus yeast artificial 
      chromosome (beta YAC), and analyzed globin gene expression in their progeny. Mice 
      carrying both the hGATA-1 and the beta YAC transgenes had normal levels of gamma- 
      and beta-globin mRNA and no distortion in the rate or in the timing of 
      gamma-to-beta switch, indicating that hGATA-1 is not involved in the 
      developmental control of gamma- and beta-globin genes. In contrast, mice carrying 
      the hGATA-1 and the beta YAC transgenes had 5- to 6-fold lower expression of the 
      human epsilon globin gene compared with beta YAC mice lacking the hGATA-1 
      transgene. These results provide direct in vivo evidence that hGATA-1 is a 
      specific repressor of human epsilon gene expression. Our findings also suggest 
      that binary transgenic mouse systems based on overexpression of transcriptional 
      factors can be used to investigate the trans control of human globin gene 
      switching. Systems as the one we describe here should be useful in the study of 
      any developmentally controlled human gene for which transgenic mice are 
      available.
FAU - Li, Q
AU  - Li Q
AD  - Division of Medical Genetics, University of Washington, Seattle 98185, USA.
FAU - Clegg, C
AU  - Clegg C
FAU - Peterson, K
AU  - Peterson K
FAU - Shaw, S
AU  - Shaw S
FAU - Raich, N
AU  - Raich N
FAU - Stamatoyannopoulos, G
AU  - Stamatoyannopoulos G
LA  - eng
GR  - R56 DK045365/DK/NIDDK NIH HHS/United States
GR  - HL20899/HL/NHLBI NIH HHS/United States
GR  - R37 DK045365/DK/NIDDK NIH HHS/United States
GR  - P01 HL053750/HL/NHLBI NIH HHS/United States
GR  - R01 HL020899/HL/NHLBI NIH HHS/United States
GR  - HL53750/HL/NHLBI NIH HHS/United States
GR  - R01 DK045365/DK/NIDDK NIH HHS/United States
GR  - DK45365/DK/NIDDK NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Erythroid-Specific DNA-Binding Factors)
RN  - 0 (GATA1 Transcription Factor)
RN  - 0 (GATA1 protein, human)
RN  - 0 (Gata1 protein, mouse)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA Probes)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 9004-22-2 (Globins)
SB  - IM
MH  - Animals
MH  - Chromosomes, Artificial, Yeast
MH  - DNA Primers
MH  - DNA-Binding Proteins/biosynthesis/*metabolism
MH  - Erythroid-Specific DNA-Binding Factors
MH  - GATA1 Transcription Factor
MH  - *Genes, Switch
MH  - Globins/biosynthesis/*genetics
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - Nuclear Proteins
MH  - Polymerase Chain Reaction
MH  - RNA Probes
MH  - RNA, Messenger/biosynthesis
MH  - Suppression, Genetic
MH  - Transcription Factors/biosynthesis/*metabolism
MH  - Transcription, Genetic
PMC - PMC20107
EDAT- 1997/03/18 00:00
MHDA- 1997/03/18 00:01
PMCR- 1997/09/18
CRDT- 1997/03/18 00:00
PHST- 1997/03/18 00:00 [pubmed]
PHST- 1997/03/18 00:01 [medline]
PHST- 1997/03/18 00:00 [entrez]
PHST- 1997/09/18 00:00 [pmc-release]
AID - 3910 [pii]
AID - 10.1073/pnas.94.6.2444 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2444-8. doi: 10.1073/pnas.94.6.2444.