ChIP-Seq analysis of Myc-tagged VEX1. VEX1 ChIP-Seq

Expression of a single allele from a large gene family is inherently stochastic rather than deterministic. This allelic exclusion effectively generates diversity and underpins immune evasion by parasitic protozoa and olfaction in mammals and insects. The molecular mechanisms that allow for activation of one allele, coordinated with the heritable exclusion of others, have remained poorly understood, however. In African trypanosomes, one telomeric and polycistronic variant surface glycoprotein (VSG) gene expression site (ES) is transcriptionally active at a time. This active VSG-ES is associated with an RNA-polymerase-I (pol-I) transcription factory, known as the expression-site body (ESB), and with VSG exclusion 1 (VEX1). Here, we identify new proteins responsible for maintaining sequestration of VEX1 at the ESB and for driving this mechanism of allelic exclusion. A transcription, VEX2 and CAF-1 dependent sequestration of VEX1 provides a ‘winner-takes-all’ paradigm for the establishment, maintenance and inheritance of nuclear bodies and allele-specific epigenetic states.