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Role of the GATA-1/FOG-1/NuRD Pathway in the Expression of Human β-Like Globin Genes.
- Source :
-
Molecular & Cellular Biology . Jul2010, Vol. 30 Issue 14, p6-6. 1p. - Publication Year :
- 2010
-
Abstract
- The human β-globin genes are expressed in a developmentally controlled fashion. Studies on the molecular mechanisms underlying the stage-specific regulation of globin genes have been fueled by the clinical benefit of elevated fetal γ-globin expression in patients with sickle cell anemia and thalassemia. Recent reports suggested a role of the hematopoietic transcription factor GATA-1, its cofactor FOG-1, and the associated chromatin remodeling complex NuRD in the developmental silencing of HBG1 and HBG2 gene expression. To examine whether FOG-1 via NuRD controls HBG1 and HBG2 silencing in vivo, we created mice in which the FOG-1/NuRD complex is disrupted (A. Miccio et al., EMBO J. 29:442-456, 2010) and crossed these with animals carrying the entire human β-globin gene locus as a transgene. We found that the FOG-1/NuRD interaction is dispensable for the silencing of human HBG1 and HBG2 expression. In addition, mutant animals displayed normal silencing of the endogenous embryonic globin genes. In contrast, a significant reduction of adult-type human and murine globin gene expression was found in adult bone marrows of mutant animals. These results suggest that, unexpectedly, NuRD is required for FOG-1-dependent activation of adult-type globin gene expression but is dispensable for human γ-globin silencing in vivo. [ABSTRACT FROM AUTHOR]
- Subjects :
- *GENES
*MOLECULAR structure
*TRANSCRIPTION factors
*SICKLE cell anemia
*THALASSEMIA
Subjects
Details
- Language :
- English
- ISSN :
- 02707306
- Volume :
- 30
- Issue :
- 14
- Database :
- Academic Search Index
- Journal :
- Molecular & Cellular Biology
- Publication Type :
- Academic Journal
- Accession number :
- 52414381
- Full Text :
- https://doi.org/10.1128/MCB.00001-10