Question

These are the questions that need to be answered for the paper "Recruitment of PfSET2 by RNA Polymerase II to Variant Antigen Encoding Loci Contributes to Antigenic Variation in P. falciparum" :

1. What is the context of the paper-background
2. Summarize big picture aspect-impact
3. What is the central hypothesis to be tested
4. FOR each figure-what are the conclusions based upon?
5. What are the controls used in each figure?
6. What is WRONG with the data/interpretation?
7. What experiment would you do to check?
8. What are the major conclusions/results
9. What other experiments do the authors propose?

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1. What is the context of the paper-background
SET2 is a methyltransferase that is plased on sites in the DNA by RNAPolII during transcription. Specifically SET2 binds to the C-terminal Domain of subunit Rpb1 and only after proper phosphorylation. Subsequently histone H3 (H3K36me3) binds to these SET2 markers anywhere in the genome that such RNAPolII transcription has taken place. An ortholog of SET2, PfSET2 found in P. falciparum is thought to provide a marker for attachment of histone H3 however the site on the chromatin is limited mainly to telomere regions and in stretches of DNA coding for multi-copy genes that exhibit variant mutually exclusive expression. This role for PfSET has been inferred because animals that have been genetically modified as Knock-outs for this gene show greatly reduced levels of H3.
Two recent disparate research findings bear on this relationship. First the C-terminal Domain in parasites infecting primates has been shown to be expanded compared to CTD in rodent parasites. Secondly epigenetic modification of antigens in rodents is thought to be significantly different from the same in primates.
Given the coincidence of these observations the authors suggest that the altered CTD is related to pfSET function in regulating mutually exclusive expression (through epigenetic modification) of the most common red blood cell antigen, var. Their findings suggest that the change in CTD in primates alters the interaction of CTD and pfSET2 such that pfSET2 can bind to the CTD when it is unphosphorylated....

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