July 24, 2017

How Epo action is ‘enhanced’

The hormone erythropoietin (Epo) controls red blood cell production and synthetic forms of Epo treat multiple disorders. New Vanderbilt research details how Epo works.

The hormone erythropoietin (Epo) controls red blood cell production. Global annual sales of synthetic Epo to treat anemia resulting from kidney disease, cancer treatment and other disorders exceed $7 billion.

Although Epo has been the focus of studies over the past several decades, precisely how Epo signaling controls erythroid expression patterns through epigenetic and transcriptional mechanisms remains poorly understood.

Reporting this month in the journal Experimental Hematology, Bryan Venters, Ph.D., and colleagues describe for the first time how Epo reprograms the “epigenome,” the chemical compounds that regulate gene expression, in erythroid cells – red blood cells in various stages of differentiation.

Using a mouse model they developed, the researchers identified a repertoire of Epo-modulated “enhancers,” short regions of DNA bound to transcription factors that increase the likelihood particular genes will be transcribed. They also identified several hundred “super-enhancers” linked to key erythroid genes.

Taken together, these findings provide a framework for studying how Epo, enhancers and transcription factors coordinate in the control of red blood cell production.

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