Q3: Molecular Deduction – Epigenetic Editing of the CDKL5 Locus In the study by Halmai et al. (2020), a dCas9-TET1 fusion was used to reactivate the silenced CDKL5 allele. Predict the outcome if an investigator replaced the TET1 "eraser" with a DNMT3A "writer" targeted to the same promoter on the active X chromosome (Xa). How would this substitution affect the total cellular "dosage" of CDKL5 protein, and why would the synergistic use of a VP64 transactivator likely fail to overcome this specific change?
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