Epigenetic regulation is a critical mechanism in controlling virulence, differentiation, and survival of the human
malaria parasite Plasmodium (P.) falciparum. Bromodomain
proteins contribute to this process by binding to acetylated
lysine residues of
histones and thereby targeting the gene regulatory machinery to gene promoters. A
protein complex containing the P. falciparum bromodomain
proteins (PfBDP) 1 and PfBDP2 (BDP1/BDP2 core complex) was previously shown to play an essential role for the correct transcription of invasion related genes. Here, we performed a functional characterization of a third component of this complex, which we dubbed PfBDP7, because structural modelling predicted a typical bromodomain fold. We confirmed that PfBDP7 is a
nuclear protein that interacts with PfBDP1 at invasion gene promoters in mature schizont stage parasites and contributes to their transcription. Although partial depletion of PfBDP7 showed no significant effect on parasite viability, conditional knock down of either PfBDP7 or PfBDP1 resulted in the de-repression of variant
surface antigens (VSA), which are important
pathogenicity factors. This de-repression was evident both on
mRNA and
protein level. To understand the underlying mechanism, we mapped the genome wide binding sites of PfBDP7 by ChIPseq and showed that in early schizonts, PfBDP7 and PfBDP1 are commonly enriched in heterochromatic regions across the gene body of all VSA families, including genes coding for PfEMP1, RIFIN, STEVOR, and PfMC-2TM. This suggests that PfBDP7 and PfBDP1 contribute to the silencing of VSAs by associating with
heterochromatin. In conclusion, we identified PfBDP7 as a
chromatin binding protein that is a constitutive part of the P. falciparum BDP1/BDP2 core complex and established PfBDP1 and PfBDP7 as novel players in the silencing of
heterochromatin regulated virulence gene families of the
malaria parasite P. falciparum.