Cohesin contributes to transcriptional repression of stage‐specific genes in the human malaria parasite

• Published in: EMBO reports Vol. 24; no. 10; p. e57090
• Main Authors: Rosa, Catarina, Singh, Parul, Chen, Patty, Sinha, Ameya, Claës, Aurélie, Preiser, Peter R, Dedon, Peter C, Baumgarten, Sebastian, Scherf, Artur, Bryant, Jessica M
• Format: Journal Article
• Language: English
• Published: Heidelberg Blackwell Publishing Ltd 09.10.2023; EMBO Press; John Wiley and Sons Inc
• Subjects: Accessibility; Antigens; Binding; Biochemistry, Molecular Biology; Chromatin; Chromosomes; Cohesin; Cohesion; Egress; Epigenetics; Erythrocytes; Gene expression; Gene silencing; Genes; Genomes; Heterochromatin; Life cycles; Life Sciences; Malaria; Molecular biology; Molecular modelling; Parasites; Plasmodium falciparum; Proteins; Vector-borne diseases; Plasmodium falciparum; cohesin; transcription; chromatin
• ISSN: 1469-221X; 1469-3178
• DOI: 10.15252/embr.202357090

Abstract The complex life cycle of the human malaria parasite, Plasmodium falciparum , is driven by specific transcriptional programs, but it is unclear how most genes are activated or silenced at specific times. There is an association between transcription and spatial organization; however, the molecular mechanisms behind genome organization are unclear. While P. falciparum lacks key genome‐organizing proteins found in metazoans, it has all core components of the cohesin complex. To investigate the role of cohesin in P. falciparum , we functionally characterize the cohesin subunit Structural Maintenance of Chromosomes protein 3 (SMC3). SMC3 knockdown during early stages of the intraerythrocytic developmental cycle (IDC) upregulates a subset of genes involved in erythrocyte egress and invasion, which are normally expressed at later stages. ChIP‐seq analyses reveal that during the IDC, SMC3 enrichment at the promoter regions of these genes inversely correlates with gene expression and chromatin accessibility. These data suggest that SMC3 binding contributes to the repression of specific genes until their appropriate time of expression, revealing a new mode of stage‐specific gene repression in P. falciparum . Synopsis image In the human malaria parasite Plasmodium falciparum , the cohesin subunit SMC3 plays a role in stage‐specific gene repression that is distinct from heterochromatin‐mediated repression of genes involved in antigenic variation and gametocytogenesis. SMC3 knockdown results in the aberrant upregulation of genes involved in egress from and invasion into the human red blood cell at times when they are normally repressed. SMC3 binding to the promoters of these genes shows an inverse relationship with their transcriptional activity and chromatin accessibility.