Cohesin contributes to transcriptional repression of stage-specific genes in the human malaria parasite.
Catarina RosaParul SinghPatty ChenAmeya SinhaAurélie ClaësPeter Rainer PreiserPeter C DedonSebastian BaumgartenArtur ScherfJessica M BryantPublished in: EMBO reports (2023)
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.
Keyphrases
- genome wide
- plasmodium falciparum
- gene expression
- dna methylation
- transcription factor
- genome wide identification
- endothelial cells
- life cycle
- copy number
- poor prognosis
- binding protein
- bioinformatics analysis
- single cell
- machine learning
- oxidative stress
- artificial intelligence
- circulating tumor cells
- cell migration
- electronic health record
- heat shock