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- W2951832004 abstract "In heterogametic organisms, expression of unequal number of X chromosomes in males and females is balanced by a process called dosage compensation. In Drosophila and mammals, dosage compensation involves nearly two-fold up-regulation of the X chromosome mediated by dosage compensation complex (DCC). Experimental studies on the role of DCC on RNA polymerase II (Pol II) transcription in mammals disclosed a non-linear relationship between Pol II densities at different transcription steps and mRNA expression. An ∼20-30% increase in Pol II densities corresponds to a rough 200% increase in mRNA expression and two-fold up-regulation. Here, using a simple kinetic model of Pol II transcription calibrated by in vivo measured rate constants of different transcription steps in mammalian cells, we demonstrate how this non-linearity can be explained by multi-step transcriptional regulation. Moreover, we show how multi-step enhancement of Pol II transcription can increase mRNA production while leaving Pol II densities unaffected. Our theoretical analysis not only recapitulates experimentally observed Pol II densities upon two-fold up-regulation but also points to erroneous interpretations of Pol II profiles from chromatin immunoprecipitation sequencing (ChIP-seq) or global run-on assays." @default.
- W2951832004 created "2019-06-27" @default.
- W2951832004 creator A5071752979 @default.
- W2951832004 date "2018-02-01" @default.
- W2951832004 modified "2023-10-03" @default.
- W2951832004 title "Multi-step regulation of transcription kinetics explains the non-linear relation between RNA polymerase II density and mRNA expression in dosage compensation" @default.
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- W2951832004 doi "https://doi.org/10.1016/j.jtbi.2017.11.004" @default.
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