Repression of human gamma-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.
Blood
; 107(5): 2138-45, 2006 Mar 01.
Article
in En
| MEDLINE
| ID: mdl-16263792
ABSTRACT
Binding of the stage selector protein (SSP) to the stage selector element (SSE) in the human gamma-globin promoter contributes to the preferential expression of the gamma-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 gamma-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 gamma-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 gamma-gene expression in K562 cells. These findings provide one potential mechanism that could contribute to the autonomous silencing of the human gamma-genes in adult erythroid cells.
Full text:
1
Database:
MEDLINE
Main subject:
Transcription Factors
/
Globins
/
Gene Silencing
/
NF-E2 Transcription Factor, p45 Subunit
/
Fetal Blood
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Blood
Year:
2006
Type:
Article
Affiliation country:
Australia