NF-Y Recruits Both Transcription Activator and Repressor to Modulate Tissue- and Developmental Stage-Specific Expression of Human Î³-Globin Gene
MetadataShow full item record
AbstractThe human embryonic, fetal and adult Î²-like globin genes provide a paradigm for tissue- and developmental stage-specific gene regulation. The fetal Î³-globin gene is expressed in fetal erythroid cells but is repressed in adult erythroid cells. The molecular mechanism underlying this transcriptional switch during erythroid development is not completely understood. Here, we used a combination of in vitro and in vivo assays to dissect the molecular assemblies of the active and the repressed proximal Î³-globin promoter complexes in K562 human erythroleukemia cell line and primary human fetal and adult erythroid cells. We found that the proximal Î³-globin promoter complex is assembled by a developmentally regulated, general transcription activator NF-Y bound strongly at the tandem CCAAT motifs near the TATA box. NF-Y recruits to neighboring DNA motifs the developmentally regulated, erythroid transcription activator GATA-2 and general repressor BCL11A, which in turn recruit erythroid repressor GATA-1 and general repressor COUP-TFII to form respectively the NF-Y/GATA-2 transcription activator hub and the BCL11A/COUP-TFII/GATA-1 transcription repressor hub. Both the activator and the repressor hubs are present in both the active and the repressed Î³-globin promoter complexes in fetal and adult erythroid cells. Through changes in their levels and respective interactions with the co-activators and co-repressors during erythroid development, the activator and the repressor hubs modulate erythroid- and developmental stage-specific transcription of Î³-globin gene.
CitationPLoS One. 2012 Oct 10; 7(10):e47175
- SCF induces gamma-globin gene expression by regulating downstream transcription factor COUP-TFII.
- Authors: Aerbajinai W, Zhu J, Kumkhaek C, Chin K, Rodgers GP
- Issue date: 2009 Jul 2
- The distinctive roles of erythroid specific activator GATA-1 and NF-E2 in transcription of the human fetal γ-globin genes.
- Authors: Woon Kim Y, Kim S, Geun Kim C, Kim A
- Issue date: 2011 Sep 1
- Genomic footprinting and sequencing of human beta-globin locus. Tissue specificity and cell line artifact.
- Authors: Reddy PM, Stamatoyannopoulos G, Papayannopoulou T, Shen CK
- Issue date: 1994 Mar 18
- The long terminal repeat (LTR) of ERV-9 human endogenous retrovirus binds to NF-Y in the assembly of an active LTR enhancer complex NF-Y/MZF1/GATA-2.
- Authors: Yu X, Zhu X, Pi W, Ling J, Ko L, Takeda Y, Tuan D
- Issue date: 2005 Oct 21
- DNA-protein interactions in the proximal zeta-globin promoter: identification of novel CCACCC- and CCAAT-binding proteins.
- Authors: Sabath DE, Koehler KM, Yang WQ, Phan V, Wilson J
- Issue date: 1998 Jun