Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Chromatin based modeling of transcription rates identifies the contribution of different regulatory layers to steady-state mRNA levels.


ABSTRACT: Messenger RNA levels in eukaryotes are balanced by two consecutive regulatory layers. Primary, transcriptional regulation at the level of chromatin and secondary, post-transcriptional regulation of the initial transcript in the cytoplasm. Each layer is individually studied in mechanistic detail, while integration of both processes is required to quantify the individual contribution to steady-state RNA levels. Here we show that chromatin features are sufficient to model transcription rate but with different sensitivities in dividing versus post mitotic cells. In both cases chromatin derived transcript levels explains over 80% of variance in measured RNA level enabling to separate transcription from different post-transcriptional processes. By further inclusion of measurements of mRNA half-life and micro RNA expression data we identify a low quantitative contribution of RNA decay by either micro RNA or general differential turnover to final mRNA levels. Together this establishes a chromatin based quantitative model for the contribution of transcriptional and posttranscriptional processes to steady-state levels of messenger RNA. Strand specific expression profiling by high throughput sequencing.

ORGANISM(S): Mus musculus

SUBMITTER: Dirk Schuebeler 

PROVIDER: E-GEOD-34473 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Tippmann Sylvia C SC   Ivanek Robert R   Gaidatzis Dimos D   Schöler Anne A   Hoerner Leslie L   van Nimwegen Erik E   Stadler Peter F PF   Stadler Michael B MB   Schübeler Dirk D  

Molecular systems biology 20120717


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  ...[more]

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