Open AccessRole of the GATA-1/FOG-1/NuRD Pathway in the Expression of Human β-Like Globin Genes
Author(s) -
Annarita Miccio,
Gerd A. Blobel
Publication year - 2010
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.00001-10
Subject(s) - biology , gene silencing , globin , transgene , transcription factor , gene expression , gene , regulation of gene expression , mutant , locus control region , microbiology and biotechnology , chromatin , genetics , enhancer
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 ofHBG1 andHBG2 gene expression. To examine whether FOG-1 via NuRD controlsHBG1 andHBG2 silencingin 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 humanHBG1 andHBG2 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 silencingin vivo .