New Finding on Trypanosomal Variant

Researchers have found evidence that supports the theory that modified DNA containing base J (beta-D-glucosyl-hydroxymethyluracil) is critically involved in the activation and silencing of genes for production of trypanosomal variant surface glycoprotein.

Trypanosomes are the flagellated parasites responsible for African sleeping sickness, a disease that affects approximately a half million people in sub-Saharan Africa. The parasites successfully avoid elimination by the immune system by changing the antigenic nature of the glycoprotein that coats their surface. The trypanosome has approximately 1,000 different genes that code for the variant surface glycoprotein (VSG), but only one at a time is expressed while the others are silenced by an unknown mechanism.

Investigators at the Marine Biological Laboratory (Woods Hole, MA, USA; www.mbl.edu) reported in the February 2005 issue of Molecular Cell that synthesis of DNA containing base J correlated with gene silencing. In addition, they identified a J binding protein containing a domain related to the SWI2/SNF2 family of chromatin remodeling proteins that was upregulated in bloodstream form cells and interacted with nuclear chromatin.

These findings support a model for VSG production in the bloodstream form of the trypanosome that relies on J-binding protein chromatin remodeling to control synthesis of DNA containing base J.




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Marine Biological Laboratory