Identification of a sequence element regulating H3K9 methylation at the ap2-g locus in Plasmodium falciparum
TL;DR
A cis-regulatory element, URE-G, that is required for high levels of H3K9 methylation at the ap2-g locus is identified and suggested a sequence-dependent mechanism for regulating heterochromatinized genes and insights into cell fate determination in malaria parasites are provided.
Abstract
Plasmodium falciparum, the causative agent of malaria, undergoes a critical cell fate switch during the erythrocytic stage, when a subset of parasites exits asexual replication and differentiates into gametocytes—the forms required for transmission. This conversion is controlled by the transcription factor AP2-G, whose expression is normally repressed by H3K9me3 marked heterochromatin. The mechanism by which this silenced state is abolished has remained unknown. Here we identify a cis-regulatory element, URE-G, that is required for high levels of H3K9 methylation at the ap2-g locus. Deletion of URE-G decreases this modification, resulting in AP2-G activation and increased gametocyte formation, without altering global heterochromatin structure. These findings suggest a sequence-dependent mechanism for regulating heterochromatinized genes and provide insights into cell fate determination in malaria parasites.