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Manipulating chromatin loops to regulate genes may offer future treatments for blood diseases
Date:6/7/2012

m sought to identify a looping factor, a protein that triggers chromatin looping. "We had a strong candidate for a looping factora molecule called Ldb1," said Deng. In the current study, Blobel and Deng made use of a specialized tool--a genetically engineered DNA binding protein called a zinc finger (ZF) protein, designed to specifically latch onto a chosen gene location.

They attached Lbd1 to a ZF, thereby tethering it to the target site in the beta-globin promoter. This caused a chromatin loop to form between the enhancer and promoter and allowed high-level gene transcription to occur.

"We showed that Ldb1 is a key factor in these long-range chromatin interactions that drive gene expression," said Blobel. "Moreover, our results suggest that chromatin looping is a cause, not an effect, of gene transcription. We will further study whether and how we can use forced chromatin looping to manipulate gene expression for scientific or therapeutic purposes."

Potential therapeutic implications: "One possible application of forced chromatin looping," added Blobel, "might be in hemoglobin diseases. For example, hematologists have a long-standing goal of reactivating dormant fetal hemoglobin genes to benefit children and adults with sickle cell anemia. It is worth testing whether our approach might force cells to produce fetal hemoglobin and treat sickle cell disease." More broadly, he added, forced chromatin looping might also enable researchers to turn off the expression of specific genes known to drive particular diseases.


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Contact: John Ascenzi
ascenzi@email.chop.edu
267-426-6055
Children's Hospital of Philadelphia
Source:Eurekalert  

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