Integrative view on how erythropoietin signaling controls transcription patterns in erythroid cells

Purpose of review Erythropoietin (EPO) is necessary and sufficient to trigger dynamic transcriptional patterns that drive the differentiation of erythroid precursor cells into mature, enucleated red cells. Because the molecular cloning and Food and Drug Administration approval for the therapeutic use of EPO over 30 years ago, a detailed understanding of how EPO works has advanced substantially. Yet, the precise epigenetic and transcriptional mechanisms by which EPO signaling controls erythroid expression patterns remains poorly understood. This review focuses on the current state of erythroid biology in regards to EPO signaling from human genetics and functional genomics perspectives. Recent findings The goal of this review is to provide an integrative view of the gene regulatory underpinnings for erythroid expression patterns that are dynamically shaped during erythroid differentiation. Here, we highlight vignettes connecting recent insights into a genome-wide association study linking an EPO mutation to anemia, a study linking EPO-signaling to signal transducer and activator of transcription 5 (STAT5) chromatin occupancy and enhancers, and studies that examine the molecular mechanisms driving topological chromatin organization in erythroid cells. Summary The genetic, epigenetic, and gene regulatory mechanisms underlying how hormone signal transduction influences erythroid gene expression remains only partly understood. A detailed understanding of these molecular pat...
Source: Current Opinion in Hematology - Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Source Type: research