Discovery: How haemoglobin genes are regulated

Thursday, 6 June, 2013

UNSW research on genetic switches could eventually lead to treatments for common blood diseases, such as sickle cell anaemia and thalassaemia.

Using gene therapy to replace defective genes with new copies is one approach to treating genetic disease. Perhaps a more practical strategy is to alter the expression of other human genes to compensate for the mutation.

A team led by UNSW Dean of Science, Professor Merlin Crossley, has identified potential new targets for the treatment of the most common genetic disorders known - the diseases of the blood, sickle cell anemia and thalassemia. 

In a paper published in the journal Molecular and Cellular Biology the researchers demonstrate that two gene repressors – termed Klf3 and Klf8 – are involved in turning embryonic haemoglobin genes off.

Humans have several haemoglobin genes. Embryonic genes are expressed early in life and produce globins that bind oxygen tightly, allowing the embryo to snatch oxygen from the mother’s blood. When a baby is born the embryonic genes are turned off and adult haemoglobin genes come on, taking over the job of transporting oxygen.

In individuals with mutations in their adult globin genes this switch means that the body is now relying on defective haemoglobin, leading to the onset of anemia.

It has been found that a few individuals with defective adult haemoglobin avoid the blood disease because their fetal globin genes stay on. So scientists the world over have been investigating how the fetal globins genes are regulated in the hope of re-activating them in adults to treat blood diseases.

Recently, a group in Harvard led by Stuart Orkin identified a gene regulatory protein BCL11A as a major repressor of the fetal globin gene – gamma globin. This may be a good target for therapeutic intervention. The identification of Klf3 and Klf8 as repressors of another early globin, epsilon, provides another avenue to attack the problem.

UNSW Science media: Deborah Smith. 9385 7307, 0478 492 060,