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A collaboration between the Drakesmith and Higgs Groups at the Medical Research Council Weatherall Institute of Molecular Medicine (MRC WIMM) has identified an ancient connection between metabolic and transcriptional control of erythropoiesis.

Abstract DNA molecule helix inside red blood drop. © Butusova Elena/Shutterstock.com

A new study, published in Nature Communications, found that two seemingly unrelated genes (Nprl3 and alpha-globin) that have been neighbours for over 500 million years, share enhancers for joint control of metabolism and red blood cell development (known as erythropoiesis). This provides a functional explanation for the deep-time co-conservation of these genes, and advances understanding of the complex process by which red blood cells develop from their precursor cells to carry out their essential oxygen-carrying role. 

In erythropoiesis, precursor cells undergo changes in metabolism and gene expression to degrade organelles and favour production of the oxygen-carrying protein haemoglobin. Preston et al approached erythropoiesis from a metabolic perspective, and used transgenic animal models developed over several years by the Higgs Group to study alpha-globin (a sub-unit of haemoglobin).

Expression of alpha-globin is highly upregulated during erythropoiesis. Most of the enhancers responsible for this are found within a neighbouring gene called Nprl3, which serves a key role in cell metabolism. The Nprl3 and alpha-globin genes have been genomically adjacent for over half a billion years (back to jawless vertebrates). 

 

Read the full story on the MRC Weatherall Institute of Molecular Medicine (WIMM) website.