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Chromatin measurements reveal contributions of synthesis and decay to steady-state mRNA levels

: Tippmann, S.C.; Ivanek, R.; Gaidatzis, D.; Scholer, A.; Hoerner, L.; Nimwegen, E. van; Stadler, P.F.; Stadler, M.B.; Schubeler, D.


Molecular systems biology 8 (2012), Art.593
ISSN: 1744-4292
Journal Article
Fraunhofer IZI ()

Messenger RNA levels in eukaryotes are controlled by multiple consecutive regulatory processes, which can be classified into two layers: primary transcriptional regulation at the chromosomal level and secondary, co- and post-transcriptional regulation of the mRNA. To identify the individual contribution of these layers to steady-state RNA levels requires separate quantification. Using mouse as a model organism, we show that chromatin features are sufficient to model RNA levels but with different sensitivities in dividing versus postmitotic cells. In both cases, chromatin-derived transcription rates explain over 80% of the observed variance in measured RNA levels. Further inclusion of measurements of mRNA half-life and microRNA expression data enabled the identification of a low quantitative contribution of RNA decay by either microRNA or general differential turnover to final mRNA levels. Together, this establishes a chromatin-based quantitative model for the contribution of transcriptional and post-transcriptional processes to steady-state levels of messenger RNA.