Networking erythropoiesis

Abstract

A relatively small cadre of lineage-restricted transcription factors largely orchestrates erythropoiesis, but how these nuclear factors interact to regulate this complex biology is still largely unknown. However, recent technological advances, such as chromatin immunoprecipitation (ChIP) paired with massively parallel sequencing (ChIP-seq), gene expression profiling, and comprehensive bioinformatic analyses, offer new insights into the intricacies of red cell molecular circuits.

Figure 1.

Model of the multiprotein complexes orchestrating gene expression or repression in erythroid cells. Comparison of GATA-1, SCL/TAL1, and LDB1 whole-genome occupancy maps with gene expression profiling data suggests that the GATA-1/SCL/TAL1–LMO2–LDB1–E2A pentameric complex, as well as a GATA-1–independent SCL/TAL-1–containing complex, largely activate gene expression. GATA-1 may also activate gene expression in coordination with KLF1 (activating complexes, green box). GATA-1 might repress gene expression via a multi-step process. Interaction with the transcriptional repressor GFI-1B recruits the LSD1/coREST complex, which results in removal of the activating H3K4me2 mark. To permanently silence gene expression, GATA-1 can recruit the PRC2 complex (EED, Ezh2, and Suz12) resulting in H3K27 trimethylation and gene repression. The SCL/TAL1 complex can recruit the corepressors ETO2 and Mtgr1 resulting in SCL/TAL1 mediated gene silencing (repressing complexes, red box).