Globin gene activation during haemopoiesis is driven by protein complexes nucleated by GATA-1 and GATA-2

摘要: How does an emerging transcriptional programme regulate individual genes as stem cells undergo lineage commitment, differentiation and maturation? To answer this, we have analysed the dynamic protein/DNA interactions across 130 kb of chromatin containing mouse α-globin cluster in representing all stages from to mature erythroblasts. The α-gene appears be inert pluripotent cells, but priming expression begins multipotent haemopoietic progenitors via GATA-2. In committed erythroid progenitors, GATA-2 is replaced by GATA-1 binding extended additional sites including promoters. Both nucleate various protein complexes SCL/LMO2/E2A/Ldb-1 NF-E2. Changes are accompanied sequential alterations long-range histone acetylation methylation. recruitment polymerase II, which ultimately leads a rapid increase transcription, occurs late maturation. These studies provide detailed evidence for more general hypothesis that commitment primarily driven appearance key factors, bind at specific, high-affinity sites.