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Background  Various transcription factors are involved in the process of mutually exclusive expression and clonal variation of the  Plasmodium  multigene ( var ) family. Recent studies revealed that a  P. falciparum  SWI/SNF-related matrix-associated actin-dependent regulator of chromatin ( PfSWIB ) might trigger stage-specific programmed cell death (PCD), and was not only crucial for the survival and development of parasite, but also had profound effects on the parasite by interacting with other unknown proteins. However, it remains unclear whether  PfSIWB  is involved in transcriptional regulation of this virulence gene and its functional properties.    Methods  A conditional knockdown system “ PfSWIB -FKBP-LID” was introduced to the parasite clone 3D7, and an integrated parasite line “ PfSWIB -HA-FKBP-LID” was obtained by drug cycling and clone screening. Growth curve analysis (GCA) was performed to investigate the growth and development of different parasite lines during 96 h  in vitro  culturing, by assessing parasitemia. Finally, we performed qPCR assays to detect  var  gene expression profiling in various comparison groups, as well as the mutually exclusive expression pattern of the  var  genes within a single 48 h life-cycle of  P. falciparum  in different parasite lines. In addition, RNA-seq was applied to analyze the  var  gene expression in different lines.    Results  GCA revealed that conditional knockdown of  PfSWIB  could interfere with the growth and development of  P. falciparum . The parasitemia of  PfSWIB∆  showed a significant decline at 96 h during  in vitro  culture compared with the  PfSWIB  and 3D7 lines ( P  < 0.0001). qPCR and RNA-seq analysis confirmed that depletion of  PfSWIB  not only silences  upsA ,  upsC  and partial  upsB var  genes, as well as removes the silencing of partial  upsB var  genes at the ring stage in  PfSWIB∆  line, but also leads to aberrant expression of  upsA  and partial  upsB/upsC var  genes at the mature stage of  P. falciparum , during a single 48-h life-cycle.    Conclusions  We demonstrated that  PfSWIB  was involved in the process of clonal variation in  var  gene expression, and crucial for the survival and development of  Plasmodium  parasite. These findings could provide better understanding of the mechanism and function of  PfSWIB  contributing to the pathogenesis in malaria parasites.

PfSWIB, a potential chromatin regulator for var gene regulation and parasite development in Plasmodium falciparum