SIP2 is the master transcription factor of <i>Plasmodium</i> merozoite formation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40117352.
- Also identified by DOI 10.1126/sciadv.ads5458 and PMC identifier 11927625.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Malaria, one of the most serious infectious diseases worldwide, is caused by the proliferation of <i>Plasmodium</i> parasites through repeated cycles of intraerythrocytic development. The parasite replicates via schizogony in host erythrocytes, producing multiple progeny merozoites that invade new erythrocytes. Although merozoite formation is the most crucial step in malaria pathogenesis, its molecular mechanism remains unclear. SIP2 is an AP2 transcription factor expressed during schizogony and is particularly conserved among erythrocyte-infecting apicomplexan parasites. Here, we reveal that SIP2 in <i>Plasmodium berghei</i> (PbSIP2) functions as the master transcription factor for merozoite formation. Conditional disruption of <i>pbsip2</i> resulted in developmental arrest before merozoite formation and notable down-regulation of merozoite-related genes. ChIP-seq showed that PbSIP2 comprehensively activated merozoite-related genes by binding to previously reported cis-regulatory elements of merozoite invasion-related genes, including the bipartite motif (TGCAN<sub>4-6</sub>GTGCA). Collectively, our results indicate that SIP2 is a transcription factor that establishes erythrocyte infectivity and may have an evolutionary origin from the common ancestor of erythrocyte-infecting apicomplexan parasites.
Medical subject headings
- Merozoites
- Protozoan Proteins
- Plasmodium berghei
- Transcription Factors