The distinctive roles of erythroid specific activator GATA-1 and NF-E2 in transcription of the human fetal ?-globin genes.

ABSTRACT: GATA-1 and NF-E2 are erythroid specific activators that bind to the ?-globin locus. To explore the roles of these activators in transcription of the human fetal stage specific ?-globin genes, we reduced GATA-1 and p45/NF-E2 using shRNA in erythroid K562 cells. GATA-1 or p45/NF-E2 knockdown inhibited the transcription of the ?-globin genes, hypersensitive site (HS) formation in the LCR and chromatin loop formation of the ?-globin locus, but histone acetylation across the locus was decreased only in the case of GATA-1 knockdown. In p45/NF-E2 knockdown cells, GATA-1 binding was maintained at the LCR HSs and ?-globin promoter, but NF-E2 binding at the LCR HSs was reduced by GATA-1 knockdown regardless of the amount of p45/NF-E2 in K562 cells. These results indicate that histone acetylation is dependent on GATA-1 binding, but the binding of GATA-1 is not sufficient for the ?-globin transcription, HS formation and chromatin loop formation and NF-E2 is required. This idea is supported by the distinctive binding pattern of CBP and Brg1 in the ?-globin locus. Furthermore GATA-1-dependent loop formation between HS5 and 3'HS1 suggests correlation between histone modifications and chromatin looping.

SUBMITTER: Woon Kim Y 

PROVIDER: S-EPMC3167640 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature