|
|
Blood, 1 March 2006, Vol. 107, No. 5, pp. 2138-2145.
Prepublished online as a Blood First Edition Paper on November 1, 2005; DOI 10.1182/blood-2005-06-2497.
 Previous Article | Table of Contents | Next Article 
RED CELLS
Repression of human  -globin gene expression by a short isoform of the NF-E4 protein is associated with loss of NF-E2 and RNA polymerase II recruitment to the promoter
Quan Zhao,
Wenlai Zhou,
Gerhard Rank,
Rosemary Sutton,
Xi Wang,
Helen Cumming,
Loretta Cerruti,
John M. Cunningham, and
Stephen M. Jane
From the Rotary Bone Marrow Research Laboratory, Royal Melbourne Hospital Research Foundation, Parkville, Australia; the State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, China; and Division of Experimental Hematology, St Jude Children's Research Hospital, Memphis, TN.
Binding of the stage selector protein (SSP) to the stage selector element (SSE) in the human  -globin promoter contributes to the preferential expression of the -gene in fetal erythroid cells. The SSP contains the transcription factor CP2 and an erythroid-specific partner, NF-E4. The NF-E4 gene encodes a 22-kDa polypeptide employing a non-AUG initiation codon. Antisera specific to NF-E4 detects this species and an additional 14 kDa protein, which initiates from an internal methionine. Enforced expression of p14 NF-E4 in the K562 fetal/erythroid cell line, and in primary erythroid cord blood progenitors, results in repression of -gene expression. Biochemical studies reveal that p14 NF-E4 interacts with CP2, resulting in diminished association of CP2 with the SSE in chromatin immunoprecipitation assays. p45 NF-E2 recruitment to the -promoter is also lost, resulting in a reduction in RNA polymerase II and TBP binding and a fall in promoter transcriptional activity. This effect is specific, as enforced expression of a mutant form of p14 NF-E4, which fails to interact with CP2, also fails to repress -gene expression in K562 cells. These findings provide one potential mechanism that could contribute to the autonomous silencing of the human -genes in adult erythroid cells.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
Another piece of the globin-switching puzzle
- Christopher Lowrey
Blood 2006 107: 1744.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
S. Harju-Baker, F. C. Costa, H. Fedosyuk, R. Neades, and K. R. Peterson
Silencing of A{gamma}-Globin Gene Expression during Adult Definitive Erythropoiesis Mediated by GATA-1-FOG-1-Mi2 Complex Binding at the -566 GATA Site
Mol. Cell. Biol.,
May 15, 2008;
28(10):
3101 - 3113.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Mankidy, D. V. Faller, R. Mabaera, C. H. Lowrey, M. S. Boosalis, G. L. White, S. A. Castaneda, and S. P. Perrine
Short-chain fatty acids induce {gamma}-globin gene expression by displacement of a HDAC3-NCoR repressor complex
Blood,
November 1, 2006;
108(9):
3179 - 3186.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
