On 2016 Mar 08, Nicholas Malmquist commented:

Thank you Dr. Soldati-Favre for your comments and highlighting the work of Dr. Ke Hu. In Chen PB, 2016 we openly discuss the possibility that PfSET7 is not necessarily a histone methyltransferase. We also provide examples from the literature of histone methyltransferase enzymes that are present in the cytosol in other organisms. After reporting PfSET7 as an active methyltransferase enzyme using histones as protein substrates, similar to the TgAKMT activity assays performed in Heaslip AT, 2011 and Sivagurunathan S, 2013, we invite our colleagues in the community, including those with an interest in parasite motility, to join us in the further exploration of the cellular function of PfSET7. Indeed, based solely on the phylogenetic analysis in Sivagurunathan S, 2013, investigating the role of PfSET7 in motility might prove fruitful. For additional information, the nomenclature "PfSET7" comes from Cui L, 2008 and is apparently unrelated to the SET7 family in Figure 1A of Sivagurunathan S, 2013.

On 2016 Mar 06, Dominique Soldati-Favre commented:

This well conducted study reports the enzymatic characterization of a Plasmodium falciparum Protein methyltransferase (PF3D71115200, referred to as PfSET7). This work is embedded in a line of research aiming at a better understanding of how histone post-translational modifications orchestrate gene expression and notably genes involved in virulence and antigenic variation. However the unexpected punctate cytoplasmic localization of PF3D71115200 in parasites from asexual blood stage, sporozoite and liver stage is not easily compatible with a function as histone methyltransferase. Indeed, published evidence of the phylogenetic and functional characterization of a Toxoplasma gondii ortholog of PF3D71115200 points in another direction. Heaslip AT, 2011 reported, the functional characterization of an apical protein lysine methyltransferase (TGME49216080, AKMT). The authors elegantly showed that TgAKMT is involved in activation of T. gondii motility. Additionally Sivagurunathan S, 2013 reported a detailed dissection of TgAKMT, along with a robust phylogenetic analysis showing that various apicomplexan AKMT orthologs form a clade distinct from other KMTs. In the phylogenetic tree presented in figure 1A, PF3D71115200 is described as an ortholog of TgAKMT, whereas not a single apicomplexan protein appears to fall within the SET7 cluster of histone methyltransferases. The work from Dr. Ke Hu is thus of considerable value to re-visit the interpretation of the data presented here, and to shed light on the potential role of PF3D71115200 in regulation of motility in P. falciparum.

On 2016 Mar 06, Dominique Soldati-Favre commented:

This well conducted study reports the enzymatic characterization of a Plasmodium falciparum Protein methyltransferase (PF3D71115200, referred to as PfSET7). This work is embedded in a line of research aiming at a better understanding of how histone post-translational modifications orchestrate gene expression and notably genes involved in virulence and antigenic variation. However the unexpected punctate cytoplasmic localization of PF3D71115200 in parasites from asexual blood stage, sporozoite and liver stage is not easily compatible with a function as histone methyltransferase. Indeed, published evidence of the phylogenetic and functional characterization of a Toxoplasma gondii ortholog of PF3D71115200 points in another direction. Heaslip AT, 2011 reported, the functional characterization of an apical protein lysine methyltransferase (TGME49216080, AKMT). The authors elegantly showed that TgAKMT is involved in activation of T. gondii motility. Additionally Sivagurunathan S, 2013 reported a detailed dissection of TgAKMT, along with a robust phylogenetic analysis showing that various apicomplexan AKMT orthologs form a clade distinct from other KMTs. In the phylogenetic tree presented in figure 1A, PF3D71115200 is described as an ortholog of TgAKMT, whereas not a single apicomplexan protein appears to fall within the SET7 cluster of histone methyltransferases. The work from Dr. Ke Hu is thus of considerable value to re-visit the interpretation of the data presented here, and to shed light on the potential role of PF3D71115200 in regulation of motility in P. falciparum.

On 2016 Mar 08, Nicholas Malmquist commented:

Thank you Dr. Soldati-Favre for your comments and highlighting the work of Dr. Ke Hu. In Chen PB, 2016 we openly discuss the possibility that PfSET7 is not necessarily a histone methyltransferase. We also provide examples from the literature of histone methyltransferase enzymes that are present in the cytosol in other organisms. After reporting PfSET7 as an active methyltransferase enzyme using histones as protein substrates, similar to the TgAKMT activity assays performed in Heaslip AT, 2011 and Sivagurunathan S, 2013, we invite our colleagues in the community, including those with an interest in parasite motility, to join us in the further exploration of the cellular function of PfSET7. Indeed, based solely on the phylogenetic analysis in Sivagurunathan S, 2013, investigating the role of PfSET7 in motility might prove fruitful. For additional information, the nomenclature "PfSET7" comes from Cui L, 2008 and is apparently unrelated to the SET7 family in Figure 1A of Sivagurunathan S, 2013.