Antigenic variation is used by the most virulent malaria parasite, Plasmodium falciparum, to evade the human immune system. The most important variant surface antigen is encoded by a family of ~60 var genes that are expressed in a mutually exclusive fashion to ensure a sustained infection. In this epigenetically-regulated process, all var genes are compacted into silent chromatin clusters at the nuclear periphery. Singular var gene activation is concomitant with chromatin decompaction and separation into an ‘activation center’. Many aspects of this complex gene regulatory system remain poorly understood, so our group is interested in discovering the chromatin-associated factors that control var gene transcription and chromatin organization.
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