This thesis has left some open questions, most of which have been already described during this discussion. There is one question that will be tested in the near future, and it is the confirmation of the readthrough of the iab-8 ncRNA (and the role of ELAV in it) as the cause of abd-A repression in PS13.
Ectopic ELAV-mediated abd-A repression
I described during this thesis how the UAShsp70ex8GFP failed to exert transcriptional interference over abd-A. I have proposed that this inability is due to the absence of splicing in this construct, and therefore the impossibility of ELAV to mediate the production of a transcriptional readthrough from this construct.
We decided to test this hypothesis by modifying the UAShsp70ex8GFP construct, introducing exon 7 and the short intron between exons 7 and 8 upstream from the modified exon 8 (Figure 45)
Figure 45 The UAShsp70ex7-8GFP construct
Schematic representation of the future UAShsp70ex7-8GFP construct.
If my hypothesis is correct, the expression of this construct in embryonic neurons should cause the splicing from its "exon 7" into abd-A, repressing abd-A by transcriptional interference. In non-neural tissue, however, exon 7 will splice efficiently into exon 8, which will cause the termination of transcription and will have no action over abd-A.
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On the other hand, co-expressing in a non-neural tissue the UAShsp70ex7-8GFP with a UAS-ELAV transgene will presumably lead to ectopic neural-like splicing, causing transcriptional interference outside of the nervous system.
Chromatin studies
The GAL4/GAL80 system developed by Welcome Bender and mentioned in the introduction can be used for the sorting of cells from a single parasegment, allowing parasegment-specific chromatin studies (Bowman et al. 2014). This will be extremely useful for the study of the chromatin state in the abd-A locus in PS13, in presence and absence of the transcription of the iab-8 ncRNA.
It would be interesting to check for the presence or absence of paused and elongated RNA polymerase in the promoter area of abd-A, comparing PS12 cells with PS13 cells. If the hypotheses based on the results showed by this thesis are correct, we can already predict the possible outcome of such a study:
- Presence of both paused and elongating RNA polymerases in the abd-A promoter area in cells extracted from PS12, in both WT and Fab-864 embryos.
- Absence of paused RNApol in PS13 of WT embryos, but presence of elongating RNApol (derived from the readthrough transcription of the iab-8 ncRNA), upstream and downstream from the promoter of abd-A.
- In Fab-864 embryos, the promoter of abd-A in PS13 will have a similar RNApol profile to the promoter of PS12.
This would provide a molecular basis to the transcriptional interference model, and demonstrate the role of the readthrough transcription of the iab-8 ncRNA in this process.
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ABBREVIATIONS
Names of genes or genotypes are written in italics.
A-P: anterior-posterior
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